document_title: DNA

question_text: where can you find dna in the body

question_tokens: where can you find dna in the body

text: DNA

text: Properties

text: DNA is a long polymer made from repeating units called nucleotides.[6][7] The structure of DNA is dynamic along its length, being capable of coiling into tight loops, and other shapes.[8] In all species it is composed of two helical chains, bound to each other by hydrogen bonds. Both chains are coiled round the same axis, and have the same pitch of 34 ångströms (3.4 nanometres). The pair of chains has a radius of 10 ångströms (1.0 nanometre).[9] According to another study, when measured in a different solution, the DNA chain measured 22 to 26 ångströms wide (2.2 to 2.6 nanometres), and one nucleotide unit measured 3.3 Å (0.33 nm) long.[10] Although each individual nucleotide repeating unit is very small, DNA polymers can be very large molecules containing millions to hundreds of millions of nucleotides. For instance, the DNA in the largest human chromosome, chromosome number 1, consists of approximately 220 million base pairs[11] and would be 85 mm long if straightened.

text: In living organisms, DNA does not usually exist as a single molecule, but instead as a pair of molecules that are held tightly together.[12][13] These two long strands entwine like vines, in the shape of a double helix. The nucleotide contains both a segment of the backbone of the molecule (which holds the chain together) and a nucleobase (which interacts with the other DNA strand in the helix). A nucleobase linked to a sugar is called a nucleoside and a base linked to a sugar and one or more phosphate groups is called a nucleotide. A polymer comprising multiple linked nucleotides (as in DNA) is called a polynucleotide.[14]

text: The backbone of the DNA strand is made from alternating phosphate and sugar residues.[15] The sugar in DNA is 2-deoxyribose, which is a pentose (five-carbon) sugar. The sugars are joined together by phosphate groups that form phosphodiester bonds between the third and fifth carbon atoms of adjacent sugar rings. These asymmetric bonds mean a strand of DNA has a direction. In a double helix, the direction of the nucleotides in one strand is opposite to their direction in the other strand: the strands are antiparallel. The asymmetric ends of DNA strands are said to have a directionality of five prime (5′) and three prime (3′), with the 5′ end having a terminal phosphate group and the 3′ end a terminal hydroxyl group. One major difference between DNA and RNA is the sugar, with the 2-deoxyribose in DNA being replaced by the alternative pentose sugar ribose in RNA.[13]

text: The DNA double helix is stabilized primarily by two forces: hydrogen bonds between nucleotides and base-stacking interactions among aromatic nucleobases.[17] In the aqueous environment of the cell, the conjugated π bonds of nucleotide bases align perpendicular to the axis of the DNA molecule, minimizing their interaction with the solvation shell. The four bases found in DNA are adenine (A), cytosine (C), guanine (G) and thymine (T). These four bases are attached to the sugar-phosphate to form the complete nucleotide, as shown for adenosine monophosphate. Adenine pairs with thymine and guanine pairs with cytosine. It was represented by A-T base pairs and G-C base pairs.[18][19]

text: Nucleobase classification

text: The nucleobases are classified into two types: the purines, A and G, being fused five- and six-membered heterocyclic compounds, and the pyrimidines, the six-membered rings C and T.[13] A fifth pyrimidine nucleobase, uracil (U), usually takes the place of thymine in RNA and differs from thymine by lacking a methyl group on its ring. In addition to RNA and DNA, many artificial nucleic acid analogues have been created to study the properties of nucleic acids, or for use in biotechnology.[20]

text: Non canonical bases

text: Uracil is not usually found in DNA, occurring only as a breakdown product of cytosine. However, in several bacteriophages, Bacillus subtilis bacteriophages PBS1 and PBS2 and Yersinia bacteriophage piR1-37, thymine has been replaced by uracil.[21] Another phage - Staphylococcal phage S6 - has been identified with a genome where thymine has been replaced by uracil.[22]

text: 5-hydroxymethyldeoxyuridine,(hm5dU) is also known to replace thymidine in several genomes including the Bacillus phages SPO1, ϕe, SP8, H1, 2C and SP82. Another modified uracil - 5-dihydroxypentauracil – has also been described.[23]

text: Base J (beta-d-glucopyranosyloxymethyluracil), a modified form of uracil, is also found in several organisms: the flagellates Diplonema and Euglena, and all the kinetoplastid genera.[24] Biosynthesis of J occurs in two steps: in the first step, a specific thymidine in DNA is converted into hydroxymethyldeoxyuridine; in the second, HOMedU is glycosylated to form J.[25] Proteins that bind specifically to this base have been identified.[26][27][28] These proteins appear to be distant relatives of the Tet1 oncogene that is involved in the pathogenesis of acute myeloid leukemia.[29] J appears to act as a termination signal for RNA polymerase II.[30][31]

text: In 1976 a bacteriophage - S-2L - which infects species of the genus Synechocystis was found to have all the adenosine bases within its genome replaced by 2,6-diaminopurine.[32] In 2016 deoxyarchaeosine was found to be present in the genomes of several bacteria and the Escherichia phage 9g.[33]

text: Modified bases also occur in DNA. The first of these recognised was 5-methylcytosine which was found in the genome of Mycobacterium tuberculosis in 1925.[34] The complete replacement of cytosine by 5-glycosylhydroxymethylcytosine in T even phages (T2, T4 and T6) was observed in 1953[35] In the genomes of Xanthomonas oryzae bacteriophage Xp12 and halovirus FH the full complement of cystosine has been replaced by 5-methylcytosine.[36][37] 6N-methyadenine was discovered to be present in DNA in 1955.[38] N6-carbamoyl-methyladenine was described in 1975.[39] 7-methylguanine was described in 1976.[40] N4-methylcytosine in DNA was described in 1983.[41] In 1985 5-hydroxycytosine was found in the genomes of the Rhizobium phages RL38JI and N17.[42] α-putrescinylthymine occurs in both the genomes of the Delftia phage ΦW-14 and the Bacillus phage SP10.[43] α-glutamylthymidine is found in the Bacillus phage SP01 and 5-dihydroxypentyluracil is found in the Bacillus phage SP15.

text: The reason for the presence of these non canonical bases in DNA is not known. It seems likely that at least part of the reason for their presence in bacterial viruses (phages) is to avoid the restriction enzymes present in bacteria. This enzyme system acts at least in part as a molecular immune system protecting bacteria from infection by viruses.

text: This does not appear to be the entire story. Four modifications to the cytosine residues in human DNA have been reported.[44] These modifications are the addition of methyl (CH3)-, hydroxymethyl (CH2OH)-, formyl (CHO)- and carboxyl (COOH)- groups. These modifications are thought to have regulatory functions.

text: Listing of non canonical bases found in DNA

text: Seventeen non canonical bases are known to occur in DNA. Most of these are modifications of the canonical bases plus uracil.

text:
Modified Adenosine

N6-carbamoyl-methyladenine
N6-methyadenine

Modified Guanine

7-Methylguanine

Modified Cytosine

N4-Methylcytosine
5-Carboxylcytosine
5-Formylcytosine
5-Glycosylhydroxymethylcytosine
5-Hydroxycytosine
5-Methylcytosine

Modified Thymidine

α-Glutamythymidine
α-Putrescinylthymine

Uracil and modifications

Base J
Uracil
5-Dihydroxypentauracil
5-Hydroxymethyldeoxyuracil

Others

Deoxyarchaeosine
2,6-Diaminopurine

text: Grooves

text: Twin helical strands form the DNA backbone. Another double helix may be found tracing the spaces, or grooves, between the strands. These voids are adjacent to the base pairs and may provide a binding site. As the strands are not symmetrically located with respect to each other, the grooves are unequally sized. One groove, the major groove, is 22 Å wide and the other, the minor groove, is 12 Å wide.[45] The width of the major groove means that the edges of the bases are more accessible in the major groove than in the minor groove. As a result, proteins such as transcription factors that can bind to specific sequences in double-stranded DNA usually make contact with the sides of the bases exposed in the major groove.[46] This situation varies in unusual conformations of DNA within the cell (see below), but the major and minor grooves are always named to reflect the differences in size that would be seen if the DNA is twisted back into the ordinary B form.

text: Base pairing

text: In a DNA double helix, each type of nucleobase on one strand bonds with just one type of nucleobase on the other strand. This is called complementary base pairing. Here, purines form hydrogen bonds to pyrimidines, with adenine bonding only to thymine in two hydrogen bonds, and cytosine bonding only to guanine in three hydrogen bonds. This arrangement of two nucleotides binding together across the double helix is called a Watson-Crick base pair. Another type of base pairing is Hoogsteen base pairing where two hydrogen bonds form between guanine and cytosine.[47] As hydrogen bonds are not covalent, they can be broken and rejoined relatively easily. The two strands of DNA in a double helix can thus be pulled apart like a zipper, either by a mechanical force or high temperature.[48] As a result of this base pair complementarity, all the information in the double-stranded sequence of a DNA helix is duplicated on each strand, which is vital in DNA replication. This reversible and specific interaction between complementary base pairs is critical for all the functions of DNA in living organisms.[7]

text: The two types of base pairs form different numbers of hydrogen bonds, AT forming two hydrogen bonds, and GC forming three hydrogen bonds (see figures, right). DNA with high GC-content is more stable than DNA with low GC-content.

text: As noted above, most DNA molecules are actually two polymer strands, bound together in a helical fashion by noncovalent bonds; this double-stranded (dsDNA) structure is maintained largely by the intrastrand base stacking interactions, which are strongest for G,C stacks. The two strands can come apart – a process known as melting – to form two single-stranded DNA (ssDNA) molecules. Melting occurs at high temperature, low salt and high pH (low pH also melts DNA, but since DNA is unstable due to acid depurination, low pH is rarely used).

text: The stability of the dsDNA form depends not only on the GC-content (% G,C basepairs) but also on sequence (since stacking is sequence specific) and also length (longer molecules are more stable). The stability can be measured in various ways; a common way is the "melting temperature", which is the temperature at which 50% of the ds molecules are converted to ss molecules; melting temperature is dependent on ionic strength and the concentration of DNA. As a result, it is both the percentage of GC base pairs and the overall length of a DNA double helix that determines the strength of the association between the two strands of DNA. Long DNA helices with a high GC-content have stronger-interacting strands, while short helices with high AT content have weaker-interacting strands.[49] In biology, parts of the DNA double helix that need to separate easily, such as the TATAAT Pribnow box in some promoters, tend to have a high AT content, making the strands easier to pull apart.[50]

text: In the laboratory, the strength of this interaction can be measured by finding the temperature necessary to break the hydrogen bonds, their melting temperature (also called Tm value). When all the base pairs in a DNA double helix melt, the strands separate and exist in solution as two entirely independent molecules. These single-stranded DNA molecules have no single common shape, but some conformations are more stable than others.[51]

text: Sense and antisense

text: A DNA sequence is called "sense" if its sequence is the same as that of a messenger RNA copy that is translated into protein.[52] The sequence on the opposite strand is called the "antisense" sequence. Both sense and antisense sequences can exist on different parts of the same strand of DNA (i.e. both strands can contain both sense and antisense sequences). In both prokaryotes and eukaryotes, antisense RNA sequences are produced, but the functions of these RNAs are not entirely clear.[53] One proposal is that antisense RNAs are involved in regulating gene expression through RNA-RNA base pairing.[54]

text: A few DNA sequences in prokaryotes and eukaryotes, and more in plasmids and viruses, blur the distinction between sense and antisense strands by having overlapping genes.[55] In these cases, some DNA sequences do double duty, encoding one protein when read along one strand, and a second protein when read in the opposite direction along the other strand. In bacteria, this overlap may be involved in the regulation of gene transcription,[56] while in viruses, overlapping genes increase the amount of information that can be encoded within the small viral genome.[57]

text: Supercoiling

text: DNA can be twisted like a rope in a process called DNA supercoiling. With DNA in its "relaxed" state, a strand usually circles the axis of the double helix once every 10.4 base pairs, but if the DNA is twisted the strands become more tightly or more loosely wound.[58] If the DNA is twisted in the direction of the helix, this is positive supercoiling, and the bases are held more tightly together. If they are twisted in the opposite direction, this is negative supercoiling, and the bases come apart more easily. In nature, most DNA has slight negative supercoiling that is introduced by enzymes called topoisomerases.[59] These enzymes are also needed to relieve the twisting stresses introduced into DNA strands during processes such as transcription and DNA replication.[60]

text: Alternative DNA structures

text: DNA exists in many possible conformations that include A-DNA, B-DNA, and Z-DNA forms, although, only B-DNA and Z-DNA have been directly observed in functional organisms.[15] The conformation that DNA adopts depends on the hydration level, DNA sequence, the amount and direction of supercoiling, chemical modifications of the bases, the type and concentration of metal ions, and the presence of polyamines in solution.[61]

text: The first published reports of A-DNA X-ray diffraction patterns—and also B-DNA—used analyses based on Patterson transforms that provided only a limited amount of structural information for oriented fibers of DNA.[62][63] An alternative analysis was then proposed by Wilkins et al., in 1953, for the in vivo B-DNA X-ray diffraction-scattering patterns of highly hydrated DNA fibers in terms of squares of Bessel functions.[64] In the same journal, James Watson and Francis Crick presented their molecular modeling analysis of the DNA X-ray diffraction patterns to suggest that the structure was a double-helix.[9]

text: Although the B-DNA form is most common under the conditions found in cells,[65] it is not a well-defined conformation but a family of related DNA conformations[66] that occur at the high hydration levels present in living cells. Their corresponding X-ray diffraction and scattering patterns are characteristic of molecular paracrystals with a significant degree of disorder.[67][68]

text: Compared to B-DNA, the A-DNA form is a wider right-handed spiral, with a shallow, wide minor groove and a narrower, deeper major groove. The A form occurs under non-physiological conditions in partly dehydrated samples of DNA, while in the cell it may be produced in hybrid pairings of DNA and RNA strands, and in enzyme-DNA complexes.[69][70] Segments of DNA where the bases have been chemically modified by methylation may undergo a larger change in conformation and adopt the Z form. Here, the strands turn about the helical axis in a left-handed spiral, the opposite of the more common B form.[71] These unusual structures can be recognized by specific Z-DNA binding proteins and may be involved in the regulation of transcription.[72]

text: Alternative DNA chemistry

text: For many years exobiologists have proposed the existence of a shadow biosphere, a postulated microbial biosphere of Earth that uses radically different biochemical and molecular processes than currently known life. One of the proposals was the existence of lifeforms that use arsenic instead of phosphorus in DNA. A report in 2010 of the possibility in the bacterium GFAJ-1, was announced,[73][73][74] though the research was disputed,[74][75] and evidence suggests the bacterium actively prevents the incorporation of arsenic into the DNA backbone and other biomolecules.[76]

text: Quadruplex structures

text: At the ends of the linear chromosomes are specialized regions of DNA called telomeres. The main function of these regions is to allow the cell to replicate chromosome ends using the enzyme telomerase, as the enzymes that normally replicate DNA cannot copy the extreme 3′ ends of chromosomes.[77] These specialized chromosome caps also help protect the DNA ends, and stop the DNA repair systems in the cell from treating them as damage to be corrected.[78] In human cells, telomeres are usually lengths of single-stranded DNA containing several thousand repeats of a simple TTAGGG sequence.[79]

text: These guanine-rich sequences may stabilize chromosome ends by forming structures of stacked sets of four-base units, rather than the usual base pairs found in other DNA molecules. Here, four guanine bases form a flat plate and these flat four-base units then stack on top of each other, to form a stable G-quadruplex structure.[81] These structures are stabilized by hydrogen bonding between the edges of the bases and chelation of a metal ion in the centre of each four-base unit.[82] Other structures can also be formed, with the central set of four bases coming from either a single strand folded around the bases, or several different parallel strands, each contributing one base to the central structure.

text: In addition to these stacked structures, telomeres also form large loop structures called telomere loops, or T-loops. Here, the single-stranded DNA curls around in a long circle stabilized by telomere-binding proteins.[83] At the very end of the T-loop, the single-stranded telomere DNA is held onto a region of double-stranded DNA by the telomere strand disrupting the double-helical DNA and base pairing to one of the two strands. This triple-stranded structure is called a displacement loop or D-loop.[81]

text:
Single branch
Multiple branches

text: Branched DNA

text: In DNA, fraying occurs when non-complementary regions exist at the end of an otherwise complementary double-strand of DNA. However, branched DNA can occur if a third strand of DNA is introduced and contains adjoining regions able to hybridize with the frayed regions of the pre-existing double-strand. Although the simplest example of branched DNA involves only three strands of DNA, complexes involving additional strands and multiple branches are also possible.[84] Branched DNA can be used in nanotechnology to construct geometric shapes, see the section on uses in technology below.

text: Chemical modifications and altered DNA packaging

text:
cytosine
5-methylcytosine
thymine

text: Base modifications and DNA packaging

text: The expression of genes is influenced by how the DNA is packaged in chromosomes, in a structure called chromatin. Base modifications can be involved in packaging, with regions that have low or no gene expression usually containing high levels of methylation of cytosine bases. DNA packaging and its influence on gene expression can also occur by covalent modifications of the histone protein core around which DNA is wrapped in the chromatin structure or else by remodeling carried out by chromatin remodeling complexes (see Chromatin remodeling). There is, further, crosstalk between DNA methylation and histone modification, so they can coordinately affect chromatin and gene expression.[85]

text: For one example, cytosine methylation produces 5-methylcytosine, which is important for X-inactivation of chromosomes.[86] The average level of methylation varies between organisms – the worm Caenorhabditis elegans lacks cytosine methylation, while vertebrates have higher levels, with up to 1% of their DNA containing 5-methylcytosine.[87] Despite the importance of 5-methylcytosine, it can deaminate to leave a thymine base, so methylated cytosines are particularly prone to mutations.[88] Other base modifications include adenine methylation in bacteria, the presence of 5-hydroxymethylcytosine in the brain,[89] and the glycosylation of uracil to produce the "J-base" in kinetoplastids.[90][91]

text: Damage

text: DNA can be damaged by many sorts of mutagens, which change the DNA sequence. Mutagens include oxidizing agents, alkylating agents and also high-energy electromagnetic radiation such as ultraviolet light and X-rays. The type of DNA damage produced depends on the type of mutagen. For example, UV light can damage DNA by producing thymine dimers, which are cross-links between pyrimidine bases.[93] On the other hand, oxidants such as free radicals or hydrogen peroxide produce multiple forms of damage, including base modifications, particularly of guanosine, and double-strand breaks.[94] A typical human cell contains about 150,000 bases that have suffered oxidative damage.[95] Of these oxidative lesions, the most dangerous are double-strand breaks, as these are difficult to repair and can produce point mutations, insertions, deletions from the DNA sequence, and chromosomal translocations.[96] These mutations can cause cancer. Because of inherent limits in the DNA repair mechanisms, if humans lived long enough, they would all eventually develop cancer.[97][98] DNA damages that are naturally occurring, due to normal cellular processes that produce reactive oxygen species, the hydrolytic activities of cellular water, etc., also occur frequently. Although most of these damages are repaired, in any cell some DNA damage may remain despite the action of repair processes. These remaining DNA damages accumulate with age in mammalian postmitotic tissues. This accumulation appears to be an important underlying cause of aging.[99][100][101]

text: Many mutagens fit into the space between two adjacent base pairs, this is called intercalation. Most intercalators are aromatic and planar molecules; examples include ethidium bromide, acridines, daunomycin, and doxorubicin. For an intercalator to fit between base pairs, the bases must separate, distorting the DNA strands by unwinding of the double helix. This inhibits both transcription and DNA replication, causing toxicity and mutations.[102] As a result, DNA intercalators may be carcinogens, and in the case of thalidomide, a teratogen.[103] Others such as benzo[a]pyrene diol epoxide and aflatoxin form DNA adducts that induce errors in replication.[104] Nevertheless, due to their ability to inhibit DNA transcription and replication, other similar toxins are also used in chemotherapy to inhibit rapidly growing cancer cells.[105]

text: Biological functions

text: DNA usually occurs as linear chromosomes in eukaryotes, and circular chromosomes in prokaryotes. The set of chromosomes in a cell makes up its genome; the human genome has approximately 3 billion base pairs of DNA arranged into 46 chromosomes.[106] The information carried by DNA is held in the sequence of pieces of DNA called genes. Transmission of genetic information in genes is achieved via complementary base pairing. For example, in transcription, when a cell uses the information in a gene, the DNA sequence is copied into a complementary RNA sequence through the attraction between the DNA and the correct RNA nucleotides. Usually, this RNA copy is then used to make a matching protein sequence in a process called translation, which depends on the same interaction between RNA nucleotides. In alternative fashion, a cell may simply copy its genetic information in a process called DNA replication. The details of these functions are covered in other articles; here the focus is on the interactions between DNA and other molecules that mediate the function of the genome.

text: Genes and genomes

text: Genomic DNA is tightly and orderly packed in the process called DNA condensation, to fit the small available volumes of the cell. In eukaryotes, DNA is located in the cell nucleus, with small amounts in mitochondria and chloroplasts. In prokaryotes, the DNA is held within an irregularly shaped body in the cytoplasm called the nucleoid.[107] The genetic information in a genome is held within genes, and the complete set of this information in an organism is called its genotype. A gene is a unit of heredity and is a region of DNA that influences a particular characteristic in an organism. Genes contain an open reading frame that can be transcribed, and regulatory sequences such as promoters and enhancers, which control transcription of the open reading frame.

text: In many species, only a small fraction of the total sequence of the genome encodes protein. For example, only about 1.5% of the human genome consists of protein-coding exons, with over 50% of human DNA consisting of non-coding repetitive sequences.[108] The reasons for the presence of so much noncoding DNA in eukaryotic genomes and the extraordinary differences in genome size, or C-value, among species, represent a long-standing puzzle known as the "C-value enigma".[109] However, some DNA sequences that do not code protein may still encode functional non-coding RNA molecules, which are involved in the regulation of gene expression.[110]

text: Some noncoding DNA sequences play structural roles in chromosomes. Telomeres and centromeres typically contain few genes but are important for the function and stability of chromosomes.[78][112] An abundant form of noncoding DNA in humans are pseudogenes, which are copies of genes that have been disabled by mutation.[113] These sequences are usually just molecular fossils, although they can occasionally serve as raw genetic material for the creation of new genes through the process of gene duplication and divergence.[114]

text: Transcription and translation

text: A gene is a sequence of DNA that contains genetic information and can influence the phenotype of an organism. Within a gene, the sequence of bases along a DNA strand defines a messenger RNA sequence, which then defines one or more protein sequences. The relationship between the nucleotide sequences of genes and the amino-acid sequences of proteins is determined by the rules of translation, known collectively as the genetic code. The genetic code consists of three-letter 'words' called codons formed from a sequence of three nucleotides (e.g. ACT, CAG, TTT).

text: In transcription, the codons of a gene are copied into messenger RNA by RNA polymerase. This RNA copy is then decoded by a ribosome that reads the RNA sequence by base-pairing the messenger RNA to transfer RNA, which carries amino acids. Since there are 4 bases in 3-letter combinations, there are 64 possible codons (43 combinations). These encode the twenty standard amino acids, giving most amino acids more than one possible codon. There are also three 'stop' or 'nonsense' codons signifying the end of the coding region; these are the TAA, TGA, and TAG codons.

text: Replication

text: Cell division is essential for an organism to grow, but, when a cell divides, it must replicate the DNA in its genome so that the two daughter cells have the same genetic information as their parent. The double-stranded structure of DNA provides a simple mechanism for DNA replication. Here, the two strands are separated and then each strand's complementary DNA sequence is recreated by an enzyme called DNA polymerase. This enzyme makes the complementary strand by finding the correct base through complementary base pairing and bonding it onto the original strand. As DNA polymerases can only extend a DNA strand in a 5′ to 3′ direction, different mechanisms are used to copy the antiparallel strands of the double helix.[115] In this way, the base on the old strand dictates which base appears on the new strand, and the cell ends up with a perfect copy of its DNA.

text: Extracellular nucleic acids

text: Naked extracellular DNA (eDNA), most of it released by cell death, is nearly ubiquitous in the environment. Its concentration in soil may be as high as 2 μg/L, and its concentration in natural aquatic environments may be as high at 88 μg/L.[116] Various possible functions have been proposed for eDNA: it may be involved in horizontal gene transfer;[117] it may provide nutrients;[118] and it may act as a buffer to recruit or titrate ions or antibiotics.[119] Extracellular DNA acts as a functional extracellular matrix component in the biofilms of several bacterial species. It may act as a recognition factor to regulate the attachment and dispersal of specific cell types in the biofilm;[120] it may contribute to biofilm formation;[121] and it may contribute to the biofilm's physical strength and resistance to biological stress.[122]

text: Cell-free fetal DNA is found in the blood of the mother, and can be sequenced to determine a great deal of information about the developing fetus.[123]

text: Interactions with proteins

text: All the functions of DNA depend on interactions with proteins. These protein interactions can be non-specific, or the protein can bind specifically to a single DNA sequence. Enzymes can also bind to DNA and of these, the polymerases that copy the DNA base sequence in transcription and DNA replication are particularly important.

text: DNA-binding proteins

text: Structural proteins that bind DNA are well-understood examples of non-specific DNA-protein interactions. Within chromosomes, DNA is held in complexes with structural proteins. These proteins organize the DNA into a compact structure called chromatin. In eukaryotes, this structure involves DNA binding to a complex of small basic proteins called histones, while in prokaryotes multiple types of proteins are involved.[124][125] The histones form a disk-shaped complex called a nucleosome, which contains two complete turns of double-stranded DNA wrapped around its surface. These non-specific interactions are formed through basic residues in the histones, making ionic bonds to the acidic sugar-phosphate backbone of the DNA, and are thus largely independent of the base sequence.[126] Chemical modifications of these basic amino acid residues include methylation, phosphorylation, and acetylation.[127] These chemical changes alter the strength of the interaction between the DNA and the histones, making the DNA more or less accessible to transcription factors and changing the rate of transcription.[128] Other non-specific DNA-binding proteins in chromatin include the high-mobility group proteins, which bind to bent or distorted DNA.[129] These proteins are important in bending arrays of nucleosomes and arranging them into the larger structures that make up chromosomes.[130]

text: A distinct group of DNA-binding proteins is the DNA-binding proteins that specifically bind single-stranded DNA. In humans, replication protein A is the best-understood member of this family and is used in processes where the double helix is separated, including DNA replication, recombination, and DNA repair.[131] These binding proteins seem to stabilize single-stranded DNA and protect it from forming stem-loops or being degraded by nucleases.

text: In contrast, other proteins have evolved to bind to particular DNA sequences. The most intensively studied of these are the various transcription factors, which are proteins that regulate transcription. Each transcription factor binds to one particular set of DNA sequences and activates or inhibits the transcription of genes that have these sequences close to their promoters. The transcription factors do this in two ways. Firstly, they can bind the RNA polymerase responsible for transcription, either directly or through other mediator proteins; this locates the polymerase at the promoter and allows it to begin transcription.[133] Alternatively, transcription factors can bind enzymes that modify the histones at the promoter. This changes the accessibility of the DNA template to the polymerase.[134]

text: As these DNA targets can occur throughout an organism's genome, changes in the activity of one type of transcription factor can affect thousands of genes.[135] Consequently, these proteins are often the targets of the signal transduction processes that control responses to environmental changes or cellular differentiation and development. The specificity of these transcription factors' interactions with DNA come from the proteins making multiple contacts to the edges of the DNA bases, allowing them to "read" the DNA sequence. Most of these base-interactions are made in the major groove, where the bases are most accessible.[46]

text: DNA-modifying enzymes

text: Nucleases and ligases

text: Nucleases are enzymes that cut DNA strands by catalyzing the hydrolysis of the phosphodiester bonds. Nucleases that hydrolyse nucleotides from the ends of DNA strands are called exonucleases, while endonucleases cut within strands. The most frequently used nucleases in molecular biology are the restriction endonucleases, which cut DNA at specific sequences. For instance, the EcoRV enzyme shown to the left recognizes the 6-base sequence 5′-GATATC-3′ and makes a cut at the horizontal line. In nature, these enzymes protect bacteria against phage infection by digesting the phage DNA when it enters the bacterial cell, acting as part of the restriction modification system.[137] In technology, these sequence-specific nucleases are used in molecular cloning and DNA fingerprinting.

text: Enzymes called DNA ligases can rejoin cut or broken DNA strands.[138] Ligases are particularly important in lagging strand DNA replication, as they join together the short segments of DNA produced at the replication fork into a complete copy of the DNA template. They are also used in DNA repair and genetic recombination.[138]

text: Topoisomerases and helicases

text: Topoisomerases are enzymes with both nuclease and ligase activity. These proteins change the amount of supercoiling in DNA. Some of these enzymes work by cutting the DNA helix and allowing one section to rotate, thereby reducing its level of supercoiling; the enzyme then seals the DNA break.[59] Other types of these enzymes are capable of cutting one DNA helix and then passing a second strand of DNA through this break, before rejoining the helix.[139] Topoisomerases are required for many processes involving DNA, such as DNA replication and transcription.[60]

text: Helicases are proteins that are a type of molecular motor. They use the chemical energy in nucleoside triphosphates, predominantly adenosine triphosphate (ATP), to break hydrogen bonds between bases and unwind the DNA double helix into single strands.[140] These enzymes are essential for most processes where enzymes need to access the DNA bases.

text: Polymerases

text: Polymerases are enzymes that synthesize polynucleotide chains from nucleoside triphosphates. The sequence of their products is created based on existing polynucleotide chains—which are called templates. These enzymes function by repeatedly adding a nucleotide to the 3′ hydroxyl group at the end of the growing polynucleotide chain. As a consequence, all polymerases work in a 5′ to 3′ direction.[141] In the active site of these enzymes, the incoming nucleoside triphosphate base-pairs to the template: this allows polymerases to accurately synthesize the complementary strand of their template. Polymerases are classified according to the type of template that they use.

text: In DNA replication, DNA-dependent DNA polymerases make copies of DNA polynucleotide chains. To preserve biological information, it is essential that the sequence of bases in each copy are precisely complementary to the sequence of bases in the template strand. Many DNA polymerases have a proofreading activity. Here, the polymerase recognizes the occasional mistakes in the synthesis reaction by the lack of base pairing between the mismatched nucleotides. If a mismatch is detected, a 3′ to 5′ exonuclease activity is activated and the incorrect base removed.[142] In most organisms, DNA polymerases function in a large complex called the replisome that contains multiple accessory subunits, such as the DNA clamp or helicases.[143]

text: RNA-dependent DNA polymerases are a specialized class of polymerases that copy the sequence of an RNA strand into DNA. They include reverse transcriptase, which is a viral enzyme involved in the infection of cells by retroviruses, and telomerase, which is required for the replication of telomeres.[77][144] For example, HIV reverse transcriptase is an enzyme for AIDS virus replication.[144] Telomerase is an unusual polymerase because it contains its own RNA template as part of its structure. It synthesizes telomeres at the ends of chromosomes. Telomeres prevent fusion of the ends of neighboring chromosomes and protect chromosome ends from damage.[78]

text: Transcription is carried out by a DNA-dependent RNA polymerase that copies the sequence of a DNA strand into RNA. To begin transcribing a gene, the RNA polymerase binds to a sequence of DNA called a promoter and separates the DNA strands. It then copies the gene sequence into a messenger RNA transcript until it reaches a region of DNA called the terminator, where it halts and detaches from the DNA. As with human DNA-dependent DNA polymerases, RNA polymerase II, the enzyme that transcribes most of the genes in the human genome, operates as part of a large protein complex with multiple regulatory and accessory subunits.[145]

text: Genetic recombination

text: A DNA helix usually does not interact with other segments of DNA, and in human cells, the different chromosomes even occupy separate areas in the nucleus called "chromosome territories".[147] This physical separation of different chromosomes is important for the ability of DNA to function as a stable repository for information, as one of the few times chromosomes interact is in chromosomal crossover which occurs during sexual reproduction, when genetic recombination occurs. Chromosomal crossover is when two DNA helices break, swap a section and then rejoin.

text: Recombination allows chromosomes to exchange genetic information and produces new combinations of genes, which increases the efficiency of natural selection and can be important in the rapid evolution of new proteins.[148] Genetic recombination can also be involved in DNA repair, particularly in the cell's response to double-strand breaks.[149]

text: The most common form of chromosomal crossover is homologous recombination, where the two chromosomes involved share very similar sequences. Non-homologous recombination can be damaging to cells, as it can produce chromosomal translocations and genetic abnormalities. The recombination reaction is catalyzed by enzymes known as recombinases, such as RAD51.[150] The first step in recombination is a double-stranded break caused by either an endonuclease or damage to the DNA.[151] A series of steps catalyzed in part by the recombinase then leads to joining of the two helices by at least one Holliday junction, in which a segment of a single strand in each helix is annealed to the complementary strand in the other helix. The Holliday junction is a tetrahedral junction structure that can be moved along the pair of chromosomes, swapping one strand for another. The recombination reaction is then halted by cleavage of the junction and re-ligation of the released DNA.[152] Only strands of like polarity exchange DNA during recombination. There are two types of cleavage: east-west cleavage and north-south cleavage. The north-south cleavage nicks both strands of DNA, while the east-west cleavage has one strand of DNA intact. The formation of a Holliday junction during recombination makes it possible for genetic diversity, genes to exchange on chromosomes, and expression of wild-type viral genomes.

text: Evolution

text: DNA contains the genetic information that allows all modern living things to function, grow and reproduce. However, it is unclear how long in the 4-billion-year history of life DNA has performed this function, as it has been proposed that the earliest forms of life may have used RNA as their genetic material.[153][154] RNA may have acted as the central part of early cell metabolism as it can both transmit genetic information and carry out catalysis as part of ribozymes.[155] This ancient RNA world where nucleic acid would have been used for both catalysis and genetics may have influenced the evolution of the current genetic code based on four nucleotide bases. This would occur, since the number of different bases in such an organism is a trade-off between a small number of bases increasing replication accuracy and a large number of bases increasing the catalytic efficiency of ribozymes.[156] However, there is no direct evidence of ancient genetic systems, as recovery of DNA from most fossils is impossible because DNA survives in the environment for less than one million years, and slowly degrades into short fragments in solution.[157] Claims for older DNA have been made, most notably a report of the isolation of a viable bacterium from a salt crystal 250 million years old,[158] but these claims are controversial.[159][160]

text: Building blocks of DNA (adenine, guanine, and related organic molecules) may have been formed extraterrestrially in outer space.[161][162][163] Complex DNA and RNA organic compounds of life, including uracil, cytosine, and thymine, have also been formed in the laboratory under conditions mimicking those found in outer space, using starting chemicals, such as pyrimidine, found in meteorites. Pyrimidine, like polycyclic aromatic hydrocarbons (PAHs), the most carbon-rich chemical found in the universe, may have been formed in red giants or in interstellar cosmic dust and gas clouds.[164]

text: Uses in technology

text: Genetic engineering

text: Methods have been developed to purify DNA from organisms, such as phenol-chloroform extraction, and to manipulate it in the laboratory, such as restriction digests and the polymerase chain reaction. Modern biology and biochemistry make intensive use of these techniques in recombinant DNA technology. Recombinant DNA is a man-made DNA sequence that has been assembled from other DNA sequences. They can be transformed into organisms in the form of plasmids or in the appropriate format, by using a viral vector.[165] The genetically modified organisms produced can be used to produce products such as recombinant proteins, used in medical research,[166] or be grown in agriculture.[167][168]

text: DNA profiling

text: Forensic scientists can use DNA in blood, semen, skin, saliva or hair found at a crime scene to identify a matching DNA of an individual, such as a perpetrator.[169] This process is formally termed DNA profiling, but may also be called "genetic fingerprinting". In DNA profiling, the lengths of variable sections of repetitive DNA, such as short tandem repeats and minisatellites, are compared between people. This method is usually an extremely reliable technique for identifying a matching DNA.[170] However, identification can be complicated if the scene is contaminated with DNA from several people.[171] DNA profiling was developed in 1984 by British geneticist Sir Alec Jeffreys,[172] and first used in forensic science to convict Colin Pitchfork in the 1988 Enderby murders case.[173]

text: The development of forensic science and the ability to now obtain genetic matching on minute samples of blood, skin, saliva, or hair has led to re-examining many cases. Evidence can now be uncovered that was scientifically impossible at the time of the original examination. Combined with the removal of the double jeopardy law in some places, this can allow cases to be reopened where prior trials have failed to produce sufficient evidence to convince a jury. People charged with serious crimes may be required to provide a sample of DNA for matching purposes. The most obvious defense to DNA matches obtained forensically is to claim that cross-contamination of evidence has occurred. This has resulted in meticulous strict handling procedures with new cases of serious crime. DNA profiling is also used successfully to positively identify victims of mass casualty incidents,[174] bodies or body parts in serious accidents, and individual victims in mass war graves, via matching to family members.

text: DNA profiling is also used in DNA paternity testing to determine if someone is the biological parent or grandparent of a child with the probability of parentage is typically 99.99% when the alleged parent is biologically related to the child. Normal DNA sequencing methods happen after birth, but there are new methods to test paternity while a mother is still pregnant.[175]

text: DNA enzymes or catalytic DNA

text: Deoxyribozymes, also called DNAzymes or catalytic DNA, are first discovered in 1994.[176] They are mostly single stranded DNA sequences isolated from a large pool of random DNA sequences through a combinatorial approach called in vitro selection or systematic evolution of ligands by exponential enrichment (SELEX). DNAzymes catalyze variety of chemical reactions including RNA-DNA cleavage, RNA-DNA ligation, amino acids phosphorylation-dephosphorylation, carbon-carbon bond formation, and etc. DNAzymes can enhance catalytic rate of chemical reactions up to 100,000,000,000-fold over the uncatalyzed reaction.[177] The most extensively studied class of DNAzymes is RNA-cleaving types which have been used to detect different metal ions and designing therapeutic agents. Several metal-specific DNAzymes have been reported including the GR-5 DNAzyme (lead-specific),[176] the CA1-3 DNAzymes (copper-specific),[178] the 39E DNAzyme (uranyl-specific) and the NaA43 DNAzyme (sodium-specific).[179] The NaA43 DNAzyme, which is reported to be more than 10,000-fold selective for sodium over other metal ions, was used to make a real-time sodium sensor in living cells.

text: Bioinformatics

text: Bioinformatics involves the development of techniques to store, data mine, search and manipulate biological data, including DNA nucleic acid sequence data. These have led to widely applied advances in computer science, especially string searching algorithms, machine learning, and database theory.[180] String searching or matching algorithms, which find an occurrence of a sequence of letters inside a larger sequence of letters, were developed to search for specific sequences of nucleotides.[181] The DNA sequence may be aligned with other DNA sequences to identify homologous sequences and locate the specific mutations that make them distinct. These techniques, especially multiple sequence alignment, are used in studying phylogenetic relationships and protein function.[182] Data sets representing entire genomes' worth of DNA sequences, such as those produced by the Human Genome Project, are difficult to use without the annotations that identify the locations of genes and regulatory elements on each chromosome. Regions of DNA sequence that have the characteristic patterns associated with protein- or RNA-coding genes can be identified by gene finding algorithms, which allow researchers to predict the presence of particular gene products and their possible functions in an organism even before they have been isolated experimentally.[183] Entire genomes may also be compared, which can shed light on the evolutionary history of particular organism and permit the examination of complex evolutionary events.

text: DNA nanotechnology

text: DNA nanotechnology uses the unique molecular recognition properties of DNA and other nucleic acids to create self-assembling branched DNA complexes with useful properties.[184] DNA is thus used as a structural material rather than as a carrier of biological information. This has led to the creation of two-dimensional periodic lattices (both tile-based and using the DNA origami method) and three-dimensional structures in the shapes of polyhedra.[185] Nanomechanical devices and algorithmic self-assembly have also been demonstrated,[186] and these DNA structures have been used to template the arrangement of other molecules such as gold nanoparticles and streptavidin proteins.[187]

text: History and anthropology

text: Because DNA collects mutations over time, which are then inherited, it contains historical information, and, by comparing DNA sequences, geneticists can infer the evolutionary history of organisms, their phylogeny.[188] This field of phylogenetics is a powerful tool in evolutionary biology. If DNA sequences within a species are compared, population geneticists can learn the history of particular populations. This can be used in studies ranging from ecological genetics to anthropology; For example, DNA evidence is being used to try to identify the Ten Lost Tribes of Israel.[189][190]

text: Information storage

text: In a paper published in Nature in January 2013, scientists from the European Bioinformatics Institute and Agilent Technologies proposed a mechanism to use DNA's ability to code information as a means of digital data storage. The group was able to encode 739 kilobytes of data into DNA code, synthesize the actual DNA, then sequence the DNA and decode the information back to its original form, with a reported 100% accuracy. The encoded information consisted of text files and audio files. A prior experiment was published in August 2012. It was conducted by researchers at Harvard University, where the text of a 54,000-word book was encoded in DNA.[191][192]

text: Moreover, in living cells, the storage can be turned active by enzymes. Light-gated protein domains fused to DNA processing enzymes are suitable for that task in vitro.[193][194] Fluorescent exonucleases can transmit the output according to the nucleotide they have read.[195]

text: History

text: DNA was first isolated by the Swiss physician Friedrich Miescher who, in 1869, discovered a microscopic substance in the pus of discarded surgical bandages. As it resided in the nuclei of cells, he called it "nuclein".[196][197] In 1878, Albrecht Kossel isolated the non-protein component of "nuclein", nucleic acid, and later isolated its five primary nucleobases.[198][199]

text: In 1909, Phoebus Levene identified the base, sugar, and phosphate nucleotide unit of the RNA (then named "yeast nucleic acid").[200][201][202] In 1929, Levene identified deoxyribose sugar in "thymus nucleic acid" (DNA).[203] Levene suggested that DNA consisted of a string of four nucleotide units linked together through the phosphate groups ("tetranucleotide hypothesis"). Levene thought the chain was short and the bases repeated in a fixed order. In 1927, Nikolai Koltsov proposed that inherited traits would be inherited via a "giant hereditary molecule" made up of "two mirror strands that would replicate in a semi-conservative fashion using each strand as a template".[204][205] In 1928, Frederick Griffith in his experiment discovered that traits of the "smooth" form of Pneumococcus could be transferred to the "rough" form of the same bacteria by mixing killed "smooth" bacteria with the live "rough" form.[206][207] This system provided the first clear suggestion that DNA carries genetic information.

text: In 1933, while studying virgin sea urchin eggs, Jean Brachet suggested that DNA is found in cell nucleus and that RNA is present exclusively in the cytoplasm. At the time, "yeast nucleic acid" (RNA) was thought to occur only in plants, while "thymus nucleic acid" (DNA) only in animals. The latter was thought to be a tetramer, with the function of buffering cellular pH.[208][209]

text: In 1937, William Astbury produced the first X-ray diffraction patterns that showed that DNA had a regular structure.[210]

text: In 1943, Oswald Avery, along with coworkers Colin MacLeod and Maclyn McCarty, identified DNA as the transforming principle, supporting Griffith's suggestion (Avery–MacLeod–McCarty experiment).[211] DNA's role in heredity was confirmed in 1952 when Alfred Hershey and Martha Chase in the Hershey–Chase experiment showed that DNA is the genetic material of the T2 phage.[212]

text: Late in 1951, Francis Crick started working with James Watson at the Cavendish Laboratory within the University of Cambridge. In 1953, Watson and Crick suggested what is now accepted as the first correct double-helix model of DNA structure in the journal Nature.[9] Their double-helix, molecular model of DNA was then based on one X-ray diffraction image (labeled as "Photo 51")[213] taken by Rosalind Franklin and Raymond Gosling in May 1952, and the information that the DNA bases are paired. On 28 February 1953 Crick interrupted patrons' lunchtime at The Eagle pub in Cambridge to announce that he and Watson had "discovered the secret of life".[214]

text: Months earlier, in February 1953, Linus Pauling and Robert Corey proposed a model for nucleic acids containing three intertwined chains, with the phosphates near the axis, and the bases on the outside.[215] Experimental evidence supporting the Watson and Crick model was published in a series of five articles in the same issue of Nature.[216] Of these, Franklin and Gosling's paper was the first publication of their own X-ray diffraction data and original analysis method that partly supported the Watson and Crick model;[63][217] this issue also contained an article on DNA structure by Maurice Wilkins and two of his colleagues, whose analysis and in vivo B-DNA X-ray patterns also supported the presence in vivo of the double-helical DNA configurations as proposed by Crick and Watson for their double-helix molecular model of DNA in the prior two pages of Nature.[64] In 1962, after Franklin's death, Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine.[218] Nobel Prizes are awarded only to living recipients. A debate continues about who should receive credit for the discovery.[219]

text: In an influential presentation in 1957, Crick laid out the central dogma of molecular biology, which foretold the relationship between DNA, RNA, and proteins, and articulated the "adaptor hypothesis".[220] Final confirmation of the replication mechanism that was implied by the double-helical structure followed in 1958 through the Meselson–Stahl experiment.[221] Further work by Crick and coworkers showed that the genetic code was based on non-overlapping triplets of bases, called codons, allowing Har Gobind Khorana, Robert W. Holley, and Marshall Warren Nirenberg to decipher the genetic code.[222] These findings represent the birth of molecular biology.[223]


document_title: 1924 Winter Olympics medal table

question_text: who won the most medals in the 1924 winter olympics

root

text: 1924 Winter Olympics medal table

text: Medal table[edit]

text: The medal table is based on information provided by the IOC and is consistent with IOC convention in its published medal tables. By default, the table is ordered by the number of gold medals the athletes from a nation have won (in this context, a nation is an entity represented by a National Olympic Committee). The number of silver medals is taken into consideration next and then the number of bronze medals. If nations are still tied, equal ranking is given and they are listed alphabetically. Two bronze medals were awarded in the 500 metres speed skating event for the third place tie.[12]

tag: p

text: *   Host nation (France)

text:
1924 Winter Olympics medal table[13]

Rank
NOC
Gold
Silver
Bronze
Total

1
 Norway (NOR)
4
7
6
17

2
 Finland (FIN)
4
4
3
11

3
 Austria (AUT)
2
1
0
3

4
 Switzerland (SUI)
2
0
1
3

5
 United States (USA)
1
2
1
4

6
 Great Britain (GBR)
1
1
2
4

7
 Sweden (SWE)
1
1
0
2

8
 Canada (CAN)
1
0
0
1

9
 France (FRA)*
0
0
3
3

10
 Belgium (BEL)
0
0
1
1

Total (10 NOCs)
16
16
17
49

tag: table


document_title: Regulatory site

question_text: which site of an enzyme is called allosteric site

text: Regulatory site

text: It has been suggested that this article be merged with Allosteric regulation. (Discuss) Proposed since October 2017.

text: This article does not cite any sources. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (December 2009) (Learn how and when to remove this template message)

text: A regulatory site (also known as an "allosteric site") is a site on an allosteric protein to which a modulator molecule (or allosteric regulator) binds. This ligand-binding site on a receptor or enzyme is distinct from the active site. Allosteric modulators alter enzyme activity by binding to the regulatory site. Some allosteric regulators activate enzymes, while others inhibit them. The working hypothesis is that when allosteric regulators bind to the regulatory site, the protein undergoes conformational changes which changes the enzyme's activity.

text:
This biochemistry article is a stub. You can help Wikipedia by expanding it.

v
t
e

text: Protein structureBiochemistry stubs

tag: ul

text: Articles to be merged from October 2017All articles to be mergedArticles lacking sources from December 2009All articles lacking sourcesAll stub articles


document_title: Democratic-Republican Party

question_text: what caused the breakup of the democratic republican party

text: Democratic-Republican Party

text: Founding[edit]

text: Congressman James Madison started the party among Representatives in Philadelphia (then the national capital) as the "Republican Party".[8] Then he, Jefferson and others reached out to include state and local leaders around the country, especially New York and the South.[9] The precise date of founding is disputed, but 1791 is a reasonable estimate and some time by 1792 is certain. The new party set up newspapers that made withering critiques of Hamiltonianism, extolled the yeoman farmer, argued for strict construction of the Constitution, favored the French Revolution, strongly opposed Great Britain and called for stronger state governments than the Federalist Party was proposing.[10]

text: Presidential elections of 1792 and 1796[edit]

text: The elections of 1792 were the first ones to be contested on anything resembling a partisan basis. In most states the congressional elections were recognized, as Jefferson strategist John Beckley put it, as a "struggle between the Treasury department and the republican interest". In New York, the candidates for governor were John Jay, a Federalist; and incumbent George Clinton, who was allied with Jefferson and the Republicans.[11] Four states' electors voted for Clinton and one (Kentucky) for Jefferson for Vice President in opposition to incumbent John Adams as well as casting their votes for President Washington. Before 1804, electors cast two votes together without differentiation as to which office was to be filled by which candidate.

text: In the 1796 election, the party made its first bid for the presidency with Jefferson as its presidential candidate and Aaron Burr as its vice presidential candidate. Jefferson came in second in the electoral college (at the time, its balloting could not distinguish between President and Vice President) and became Vice President. He would become a consistent and strong opponent of the policies of the John Adams administration. Jefferson and Madison were deeply upset by the unconstitutionality of the Alien and Sedition Acts of 1798 and they secretly wrote the Kentucky and Virginia Resolutions, which called on state legislatures to nullify unconstitutional laws. However, the other states did not follow suit and several rejected the notion that states could nullify federal law. The Republican critique of federalism became wrapped in the slogan of "Principles of 1798", which became the hallmark of the party. The most important of these principles were states' rights, opposition to a strong national government, distrust of the federal courts and opposition to the navy and the national bank. The party saw itself as a champion of republicanism and denounced the Federalists as supporters of monarchy and aristocracy.[12]

text: The party coalesced around Jefferson, who diligently maintained extensive correspondence with like-minded Republican leaders throughout the country. Washington frequently decried the growing sense of "party" emerging from the internal battles among Jefferson, Madison, Hamilton, Adams and others in his administration. As warfare in Europe increased, the two factions increasingly made foreign policy the central political issue of the day. The Republicans wanted to maintain the 1778 alliance with France, which had overthrown the monarchy and aristocracy and become a republic. Even though Britain was by far United States' leading trading partner, Republicans feared that increased trade would undermine republicanism. The Republicans distrusted Hamilton's national bank and rejected his premise that a national debt was good for the country as Republicans said they were both forms of corruption. They strongly distrusted the elitism of Hamilton's circle, denouncing it as "aristocratic"; and they called for states' rights lest the Federalists centralize ever more power in the national governments.[13] The intense debate over the Jay Treaty in 1794–1795 transformed those opposed to Hamilton's policies from a loose movement into a true political party. To fight the treaty, the Jeffersonians "established coordination in activity between leaders at the capital, and leaders, actives and popular followings in the states, counties and towns".[14] However, they were defeated when Washington mobilized public opinion in favor of the treaty.

text: Strength in Congress over time[edit]

text: Historians have used statistical techniques to estimate the party breakdown in Congress. Many Congressmen were hard to classify in the first few years, but after 1796 there was less uncertainty.

text:
Federalist and Democratic-Republican strength in Congress by election year[15]

Election year

House
1788
1790
1792
1794
1796
1798
1800
1802
1804
1806

Federalist
37
39
51
47
57
60
38
39
25
24

Republican
28
30
54
59
49
46
65
103
116
118

Percentage Republican
43%
43%
51%
56%
46%
43%
63%
73%
82%
83%

Senate
1788
1790
1792
1794
1796
1798
1800
1802
1804
1806

Federalist
18
16
16
21
22
22
15
9
7
6

Republican
8
13
14
11
10
10
17
25
17
28

Percentage Republican
31%
45%
47%
34%
31%
31%
53%
74%
71%
82%

text: The affiliation of many Congressmen in the earliest years is an assignment by later historians; these were slowly coalescing groups with initially considerable independent thinking and voting. Cunningham noted that only about a quarter of the House of Representatives up until 1794 voted with Madison as much as two-thirds of the time and another quarter against him two-thirds of the time, leaving almost half as fairly independent. Albert Gallatin recalled only two caucuses on legislative policy between 1795 and 1801, one over appropriations for Jay's Treaty and the other over the Quasi-War, but in neither case did the party decide to vote unanimously.[16]

text: Organizational strategy[edit]

text: The new party invented some of the campaign and organizational techniques which were later adopted by the Federalists and became standard American practice. It was especially effective in building a network of newspapers in major cities to broadcast its statements and editorialize its policies.[17] Fisher Ames, a leading Federalist, used the term "Jacobin" to link members of Jefferson's party to the radicals of the French Revolution. He blamed the newspapers for electing Jefferson and wrote they were "an overmatch for any Government.... The Jacobins owe their triumph to the unceasing use of this engine; not so much to skill in use of it as by repetition".[18]

text: As one historian explained: "It was the good fortune of the Republicans to have within their ranks a number of highly gifted political manipulators and propagandists. Some of them had the ability... to not only see and analyze the problem at hand but to present it in a succinct fashion; in short, to fabricate the apt phrase, to coin the compelling slogan and appeal to the electorate on any given issue in language it could understand". Outstanding propagandists included editor William Duane (1760–1835) and party leaders Albert Gallatin, Thomas Cooper and Jefferson himself.[19] Just as important was effective party organization of the sort that John J. Beckley pioneered. In 1796, he managed the Jefferson campaign in Pennsylvania, blanketing the state with agents who passed out 30,000 hand-written tickets, naming all 15 electors (printed tickets were not allowed). Beckley told one agent: "In a few days a select republican friend from the City will call upon you with a parcel of tickets to be distributed in your County. Any assistance and advice you can furnish him with, as to suitable districts & characters, will I am sure be rendered". Beckley was the first American professional campaign manager and his techniques were quickly adopted in other states.[20]

text: The emergence of the new organizational strategies can be seen in the politics of Connecticut around 1806, which have been well documented by Cunningham. The Federalists dominated Connecticut, so the Republicans had to work harder to win. In 1806, the state leadership sent town leaders instructions for the forthcoming elections. Every town manager was told by state leaders "to appoint a district manager in each district or section of his town, obtaining from each an assurance that he will faithfully do his duty". Then the town manager was instructed to compile lists and total the number of taxpayers and the number of eligible voters, find out how many favored the Republicans and how many the Federalists and to count the number of supporters of each party who were not eligible to vote but who might qualify (by age or taxes) at the next election. These highly detailed returns were to be sent to the county manager and in turn were compiled and sent to the state manager. Using these lists of potential voters, the managers were told to get all eligible people to town meetings and help the young men qualify to vote. The state manager was responsible for supplying party newspapers to each town for distribution by town and district managers.[21] This highly coordinated "get-out-the-vote" drive would be familiar to modern political campaigners, but was the first of its kind in world history.

text: Revolution of 1800[edit]

text: The party's electors secured a majority in the 1800 election, but an equal number of electors cast votes for Jefferson and Aaron Burr. The tie sent the election to the House and Federalists there blocked any choice. Hamilton, believing that Burr would be a poor choice for president, intervened and let Jefferson win, a move that would result in the collapse of the Federalist Party and Hamilton's death four years later at the hands of Burr himself in a pistol duel. Starting in 1800 in what Jefferson called the "Revolution of 1800", the party took control of the presidency and both houses of Congress, beginning a quarter century of control of those institutions. A faction called "Old Republicans" opposed the nationalism that grew popular after 1815 as they were stunned when party leaders started a Second Bank of the United States in 1816. The first official Republican Congressional Caucus meeting took place at Marache's boarding house on May 11, 1800 in Philadelphia. The January 26, 1799 letter Thomas Jefferson wrote to Elbridge Gerry became the party's platform.

text: In the Senate chamber on February 25, 1804, a "Convention of Republican members of both houses of Congress" met. Senator Stephen Bradley presided, a Committee on Presidential Electors was formed and it was resolved that Thomas Jefferson be nominated for President and George Clinton be nominated Vice President. The party held a convention by the same name on January 23, 1808, again in the Senate chamber at 6:00 pm on a Saturday. Senator Stephen Bradley, who was the President pro tempore of the Senate, again served as President of the convention with Representative Richard Johnson as the Secretary. A Committee on Correspondence was formed, James Madison was nominated for President and George Clinton was re-nominated for Vice President.

text: Legislative issues were handled by the Committee of the Whole and the elected Speaker of the House of Representatives and floor leaders, who at that time were the Chairman for the Committee on Ways and Means of the House of Representatives and Chairman for the Committee on Finance of the Senate. The state legislatures often instructed Members of Congress how to vote on specific issues. More exactly, they "instructed" the Senators (who were elected by the legislatures) and "requested" the Representatives (who were elected by the people). On rare occasions a Senator resigned rather than follow instructions. The opposition Federalist Party quickly declined, suffering from a lack of leadership after the death of Hamilton and the retirement of John Adams. It revived briefly in opposition to the War of 1812, but the extremism of its Hartford Convention of 1815 utterly destroyed it as a political force.

text: National debt[edit]

text: Jefferson and Albert Gallatin focused on the danger that the public debt, unless it was paid off, would be a threat to republican values. They were appalled that Hamilton was increasing the national debt and using it to solidify his Federalist base. Gallatin was the Republican Party's chief expert on fiscal issues and as Treasury Secretary under Jefferson and Madison worked hard to lower taxes and lower the debt, while at the same time paying cash for the Louisiana Purchase and funding the War of 1812. Burrows says of Gallatin:

text: His own fears of personal dependency and his small shopkeeper's sense of integrity, both reinforced by a strain of radical republican thought that originated in England a century earlier, convinced him that public debts were a nursery of multiple public evils—corruption, legislative impotence, executive tyranny, social inequality, financial speculation, and personal indolence. Not only was it necessary to extinguish the existing debt as rapidly as possible, he argued, but Congress would have to ensure against the accumulation of future debts by more diligently supervising government expenditures.[22]

text: However, after examining at Jefferson's direction the economic structures that Hamilton had created, Gallatin reported:

text: I have found the most perfect system ever formed, and any change that should be made, would only injure it - Hamilton made no blunders, commited no frauds - he did nothing wrong.[23]

text: Fear of a large debt is a major legacy of the party. Andrew Jackson believed the national debt was a "national curse" and he took special pride in paying off the entire national debt in 1835.[24] Politicians ever since have used the issue of a high national debt to denounce the other party for profligacy and a threat to fiscal soundness and the nation's future.[25]

text: Monroe and Adams (1816–1828)[edit]

text: In rapidly expanding western states, the Federalists had few supporters. Every state had a distinct political geography that shaped party membership. In Pennsylvania, the Republicans were weakest around Philadelphia and strongest in Scots-Irish settlements in the west. Members came from all social classes, but came predominantly from the poor, subsistence farmers, mechanics and tradesmen.[26] After the War of 1812, partisanship subsided across the young republic—people called it the Era of Good Feelings. James Monroe narrowly won the party's nomination for President in Congress over William Crawford in 1816 and defeated Federalist Rufus King in the general election.

text: In the early years of the party, the key central organization grew out of caucuses of Congressional leaders in Washington. However, the key battles to choose electors occurred in the states, not in the caucus. In many cases, legislatures still chose electors; and in others, the election of electors was heavily influenced by local parties that were heavily controlled by relatively small groups of officials. Without a significant Federalist opposition, the need for party unity was greatly diminished and the party's organization faded away.

text: James Monroe ran under the party's banner in the 1820 election and built support by consensus. Monroe faced no serious rival and was nearly unanimously elected by the electoral college. The party's historic domination by the Virginian delegation faded as New York and Pennsylvania became more important. In the 1824 election, most of the party in Congress boycotted the caucus; only a small rump group backed William Crawford. The Crawford faction included most "Old Republicans"—those who remained committed to states' rights and the Principles of 1798 and were distrustful of the nationalizing program promoted by Henry Clay and John C. Calhoun.

text: Thomas Jefferson wrote on the state of party politics in the early 1820s:[27]

text: An opinion prevails that there is no longer any distinction, that the republicans & Federalists are completely amalgamated but it is not so. The amalgamation is of name only, not of principle. All indeed call themselves by the name of Republicans, because that of Federalists was extinguished in the battle of New Orleans. But the truth is that finding that monarchy is a desperate wish in this country, they rally to the point which they think next best, a consolidated government. Their aim is now therefore to break down the rights reserved by the constitution to the states as a bulwark against that consolidation, the fear of which produced the whole of the opposition to the constitution at its birth. Hence new Republicans in Congress, preaching the doctrines of the old Federalists, and the new nick-names of Ultras and Radicals. But I trust they will fail under the new, as the old name, and that the friends of the real constitution and union will prevail against consolidation, as they have done against monarchism. I scarcely know myself which is most to be deprecated, a consolidation, or dissolution of the states. The horrors of both are beyond the reach of human foresight.

text: In the aftermath of the disputed 1824 presidential election, the separate factions took on many characteristics of parties in their own right. Adams' supporters, in league with Clay, favored modernization, banks, industrial development and federal spending for roads and other internal improvements, which the Old Republicans and the Jackson men usually opposed. Writing in his personal journal on December 13, 1826, President Adams noted the difficulty he faced in attempting to be nonpartisan in appointing men to office:[28]

text: And it is upon the occasion of appointments to office that all the wormwood and the gall of the old party hatred ooze out. Not a vacancy to any office occurs but there is a distinguished federalist started and pushed home as a candidate to fill it—always well qualified, sometimes in an eminent degree, and yet so obnoxious to the Republican party that he cannot be appointed without exciting a vehement clamor against him and against the Administration. It becomes thus impossible to fill any appointment without offending one-half the community—the federalists, if their associate is overlooked; the Republicans, if he is preferred.

text: Presidential electors were now all chosen by direct election, except in South Carolina, where the state legislatures chose them. White manhood suffrage was the norm throughout the West and in most of the East as well. The voters thus were much more powerful, and to win their votes required complex party organization. Under the leadership of Martin Van Buren, a firm believer in political organization, the Jacksonians built strong state and local organizations throughout the country. The Old Republicans, or "Radicals", mostly supported Jackson and joined with supporters of incumbent Vice President Calhoun in an alliance. President Adams was defeated by Andrew Jackson in the election of 1828.

text: Republican Party name[edit]

text: Political parties were new in the United States, and people were not accustomed to having formal names for them. There was no single, official name for the party. Party members generally called themselves "Republicans" and voted for what they called the "Republican party", "republican ticket" or "republican interest".[29] Jefferson and Madison often used the terms "republican" and "Republican party" in their letters.[30] The 1804 Convention of Republican members of Congress that renominated Jefferson described itself as a "regular republican caucus". The name Democratic-Republican was used by contemporaries only occasionally.[31]

text: The term "republican" was in widespread usage from the 1770s to describe the type of government the break-away colonies wanted to form: a republic of three separate branches of government derived from some principles and structure from ancient republics; especially the emphasis on civic duty and the opposition to corruption, elitism, aristocracy and monarchy.[32] The word is used in the United States Constitution.[33]

text: Legacy[edit]

text: A split appeared in the then Republican party during the 1824 elections (at the end of the Monroe administration). When the election was thrown to the House of Representatives, Henry Clay backed John Quincy Adams to deny the presidency to Andrew Jackson, a longtime political rival. Jackson defeated Adams in 1828 and in the next election the first Democratic national convention took place in Baltimore, Maryland on May 21–23, 1832. It nominated Andrew Jackson for a second term and he went on to win the presidential election.

text: The Adams/Clay alliance became the basis of the National Republican Party, a rival to the Jackson's Democracy and one of the successors of the Democratic-Republican Party. This party favored a higher tariff in order to protect U.S. manufacturers, as well as public works, especially roads. Many former members of the defunct Federalist Party, including Daniel Webster, joined the party. After Clay's defeat by Jackson in the 1832 presidential election, the National Republicans were absorbed into the Whig Party, a diverse group of Jackson opponents. Taking a leaf from the Jacksonians, the Whigs tended to nominate non-ideological war heroes as their presidential candidates. The Whig party fell apart in the 1850s over the question of whether to allow the expansion of slavery into new territories.

text: The modern Republican Party was formed in 1854 to oppose the expansion of slavery. Many former Whig party leaders (such as Abraham Lincoln – modern Republican Party supporters still sometimes refer to themselves as "the party of Lincoln") and former Free Soil Party leaders joined the newly formed anti-slavery party.[34] The party sought to combine Jefferson's ideals of liberty and equality with Clay's program of using an active government to modernize the economy.[35]

text: Presidents[edit]

text: Four United States Presidents were elected following a process that selected them as a national nominee of the Democratic-Republican party.

text:
#
Name
Portrait
State
Presidency
start date
Presidency
end date

3
Thomas Jefferson

Virginia
March 4, 1801
March 4, 1809

4
James Madison

Virginia
March 4, 1809
March 4, 1817

5
James Monroe

Virginia
March 4, 1817
March 4, 1825

6
John Quincy Adams

Massachusetts
March 4, 1825
March 4, 1829

text: Electoral history[edit]

text: Presidential elections[edit]

text:
Election
Candidate
Running mate
Votes
Vote %
Electoral votes
+/-
Outcome of election

1796
Thomas Jefferson[a]
Aaron Burr[b]
31,115
46.6

68 / 138

New
Lost

1800
41,330
61.4

73 / 138

 5
Victory

1804
George Clinton
104,110
72.8

162 / 176

 89
Victory

1808
James Madison
124,732
64.7

122 / 176

 40
Victory

1812
Elbridge Gerry
140,431
50.4

128 / 217

 95
Victory

DeWitt Clinton[c]
Jared Ingersoll
132,781
47.6

89 / 217

Lost

1816
James Monroe
Daniel D. Tompkins
76,592
68.2

183 / 217

 34
Victory

1820
87,343
80.6

231 / 232

 55
Victory

1824[d]
Andrew Jackson
John C. Calhoun
151,271
41.4

99 / 261

 30
Lost

John Quincy Adams
113,122
30.9

84 / 261

Victory

William H. Crawford
Nathaniel Macon
40,856
11.2

41 / 261

Lost

Henry Clay
Nathan Sanford
47,531
13

37 / 261

Lost

text:
Jump up ^ In his first presidential run, Jefferson did not win the presidency, and Burr did not win the vice presidency. However, under the pre-12th Amendment election rules, Jefferson won the vice presidency due to dissension among Federalist electors.
Jump up ^ In their second presidential run, Jefferson and Burr received the same number of electoral votes. Jefferson was subsequently chosen as President by the House of Representatives.
Jump up ^ While commonly labeled as the Federalist candidate, Clinton technically ran as a Democratic-Republican and was not nominated by the Federalist party itself, the latter simply deciding not to field a candidate. This did not prevent endorsements from state Federalist parties (such as in Pennsylvania), but he received the endorsement from the New York state Democratic-Republicans as well.
Jump up ^ William H. Crawford and Albert Gallatin were nominated for president and vice-president by a group of 66 Congressmen that called itself the "Democratic members of Congress".[36] Gallatin later withdrew from the contest. Andrew Jackson, John Quincy Adams and Henry Clay ran as Republicans, although they were not nominated by any national body. While Jackson won a plurality in the electoral college and popular vote, he did not win the constitutionally required majority of electoral votes to be elected president. The contest was thrown to the House of Representatives, where Adams won with Clay's support. The electoral college chose John C. Calhoun for vice president.

tag: ol

text: Congressional elections[edit]

text:
United States
House of Representatives

Election year
No. of
overall seats won
+/–
House Speaker

1794

59 / 105

New
Jonathan Dayton

1796

49 / 106

 10

1798

46 / 106

 3
Theodore Sedgwick

1800

68 / 106

 22
Nathaniel Macon

1802

103 / 142

 35

1804

114 / 142

 11

1806

116 / 142

 2
Joseph Bradley Varnum

1808

94 / 142

 22

1810

107 / 143

 13
Henry Clay

1812

114 / 182

 7

1814

119 / 183

 5

1816

145 / 185

 26

1818

162 / 186

 15

1820

155 / 187

 5
Philip Barbour

1822

189 / 213

 34
Henry Clay

United States
Senate

Election year
No. of
overall seats won
+/–
Senate President

1794/1795

10 / 30

New
John Adams

1796/1797

10 / 32

 0
Thomas Jefferson

1798/1799

9 / 32

 1

1800/1801

15 / 32

 6
Aaron Burr

1802/1803

22 / 32

 7

1804/1805

27 / 34

 18
George Clinton

1806/1807

28 / 34

 1

1808/1809

26 / 34

 2

1810/1811

27 / 34

 1

1812/1813

28 / 36

 1
Elbridge Gerry

1814/1815

22 / 36

 6

1816/1817

25 / 36

 3
Daniel D. Tompkins

1818/1819

30 / 42

 5

1820/1821

39 / 46

 9

1822/1823

33 / 48

 6


document_title: My Next Guest Needs No Introduction with David Letterman

question_text: when will the next episode of my next guest needs no introduction

text: Production[edit]

text: Development[edit]

text: On August 8, 2017, it was announced that Netflix had ordered a six-episode interview series starring David Letterman. Each hour-long episode will feature Letterman conducting a longform conversation with a single guest and in-the-field segments, in which he will explore topics on his own.[1][2]

text: On January 5, 2018, Netflix released further information about the series. It was announced that Letterman's guests in the first season would include Barack Obama, George Clooney, Malala Yousafzai, Jay-Z, Tina Fey, and Howard Stern. It was also announced that the series would premiere on January 12, 2018 with Letterman's interview with Obama. This interview was Obama's first since leaving office.[3][4]

text: Music[edit]

text: The show's theme song and bridging music were written and recorded by Letterman's long-time bandleader, Paul Shaffer.[5] Soon after it was announced publicly that Netflix had given the series an order, Shaffer received a phone call from Letterman asking him to work on the show. Soon after, Shaffer began to receive cuts of episodes from the first season and he started to put music in afterwards where the director thought it was needed.

text: In developing the sound of the show's music, Shaffer initially looked to Letterman for guidance. Finding none, he remembered he and Letterman's shared love for the sort of music produced at the Muscle Shoals Sound Studio in Sheffield, Alabama describing it as "the honesty you hear, the southern soul feeling." The score initially included drums but the show's producers and director thought that the music should "feel like it's Dave's old friend Paul playing." so it was ultimately stripped down to solely include piano, organ, and bass guitar.[6]

text: Episodes[edit]

text:
No.
Title
Featured guest
Original release date

1
"It's a Whole New Ball Game Now"
Barack Obama
January 12, 2018 (2018-01-12)

Cold open: Letterman interviewing Obama on Late Show with David Letterman.
On-location segment: Walking with Congressman John Lewis across the Edmund Pettus Bridge, site of the civil rights movement's Bloody Sunday in 1965.

2
"You Be the Newsman, I'll Be Liz Taylor"
George Clooney
February 9, 2018 (2018-02-09)

Cold open: Letterman and Clooney outside of LAX watching planes land and eating fast food.
On-location segment: At the home of Nick Clooney meeting Iraqi refugee Hazim Avdal whom the Clooney family is sponsoring.

3
"You Know, She Has a Nobel Peace Prize"
Malala Yousafzai
March 9, 2018 (2018-03-09)

Cold open: Letterman accompanies Yousafzai as she leads a tour group at Lady Margaret Hall, Oxford.
On-location segment: Yousafzai continues to lead the tour group as Letterman tags along, the pair browse in the University of Oxford shop, and Letterman eats lunch with Yousafzai's father.

4
"I Had a Paper Route Too"
Jay-Z
April 6, 2018 (2018-04-06)

Cold open: None
On-location segment: Letterman visits Shangri La Studio, speaks with music producer Rick Rubin and listens to Madison Ryann Ward recording.

5
"TBA"
Tina Fey
May 4, 2018[7]

6
"TBA"
Howard Stern
May 31, 2018[8]

text: Reception[edit]

text: The first season of My Next Guest Needs No Introduction has been met with a positive response from critics. On the review aggregation website Rotten Tomatoes, the first season holds a 80% approval rating with an average rating of 6.4 out of 10 based on 25 reviews.[9] Metacritic, which uses a weighted average, assigned the season a score of 70 out of 100 based on 13 reviews, indicating "generally favorable reviews".[10]


document_title: The Flight of the Phoenix (1965 film)

question_text: where was the original flight of the phoenix filmed

text: The Flight of the Phoenix (1965 film)

text: Plot[edit]

text: Frank Towns (James Stewart) is the pilot of a twin-engine Fairchild C-82 Packet cargo plane flying from Jaghbub to Benghazi in Libya; Lew Moran (Richard Attenborough) is the navigator. The passengers include Capt. Harris (Peter Finch) and Sgt. Watson (Ronald Fraser) of the British Army; Dr. Renaud (Christian Marquand), a physician; Heinrich Dorfmann (Hardy Krüger), a German aeronautical engineer; and an oil company accountant named Standish (Dan Duryea). There are also several oil workers, including Trucker Cobb (Ernest Borgnine), a mentally-disturbed foreman; Ratbags Crow (Ian Bannen), a mean-spirited, sardonic Scot; Carlos (Alex Montoya) and his pet monkey; and Gabriel (Gabriele Tinti).

text: A sudden sandstorm disables the engines, forcing Towns to crash-land in the desert. As the aircraft careens to a stop, several oil drums and oil drilling tools break loose and severely injure Gabriel's leg. Two other workers are killed.

text: The radio is unusable, but the survivors are too far off-course to be found and rescued. They have a large quantity of dates for food, but their water will last for only ten to fifteen days even if they avoid physical exertion. Harris and Carlos attempt to walk to an oasis. Carlos leaves his monkey behind with the men. Harris and Towns refuse to let Cobb go along, but Cobb defiantly follows and dies. Days later, Harris returns to the crash site alone and barely alive.

text: Meanwhile, Dorfmann has been working on a radical idea: He believes they can build a new aircraft from the wreckage. The C-82 has twin booms extending rearwards from each engine and connected by the horizontal stabilizer. Dorfmann's plan is to attach the outer sections of the both wings to the left engine and left boom, discarding the center fuselage and both inner wing sections of the aircraft. The passengers will ride on top of the wings. Harris and Moran believe he is either joking or delusional. The argument is complicated by a personality clash between Towns, a proud old traditionalist aviator, and Dorfmann, an equally proud young technician. Moran struggles to keep the peace.

text: Although Towns is resistant, Renaud points out that activity and any hope will keep the men's morale up, and so Towns agrees with the plan. Dorfmann supervises the reconstruction, while Towns remains doubtful. During the work, Gabriel commits suicide by slitting his wrist, making the men so depressed that they contemplate giving up the new plane's construction. Dorfmann is caught exceeding his water ration, but explains that he alone has been working continuously, and promises to not do it again while demanding they all work equally hard. Moran talks Towns into resuming work on the aircraft.

text: When the new aircraft is almost complete, Standish labels it "The Phoenix" after the mythical bird that is reborn from its ashes. Any good mood, however, is quashed after a band of natives comes nearby. While the others (and the aircraft) remain hidden, Harris and Renaud go to ask them for help – and are murdered. Additionally, Towns and Moran learn that Dorfmann designs model airplanes rather than full-sized ones. Dorfmann claims that the principles are exactly the same, and that in many aspects models require much more exacting designs and can be less forgiving than full-size aircraft, but Towns and Moran are horrified at the idea of flying a plane made by a man who works with "toys". Without any other choice, however, they decide to forge ahead with the plan.

text: Just as the water supplies are exhausted, the Phoenix is completed. Only seven starter cartridges are available for the engine, and the first four startup attempts are unsuccessful. Towns decides to fire the fifth cartridge with the ignition off, to clear the engine's cylinders, which he does over Dorfmann's strenuous objection. The next startup is successful. The men pull the Phoenix to a nearby hilltop and climb onto the wings. When Towns guns the engine, the Phoenix slides down the hill and along a lake bed before taking off. After landing at an oasis with a manned oil rig, the men celebrate and Towns and Dorfmann are reconciled.

text: Cast[edit]

text:
James Stewart as Capt. Frank Towns
Richard Attenborough as Lew Moran
Hardy Krüger as Heinrich Dorfmann
Peter Finch as Capt. Harris
Ernest Borgnine as Trucker Cobb
Ian Bannen as "Ratbags" Crow
Ronald Fraser as Sgt. Watson
Christian Marquand as Dr. Renaud
Dan Duryea as Standish
George Kennedy as Mike Bellamy
Gabriele Tinti as Gabriel
Alex Montoya as Carlos
Peter Bravos as Tasso
William Aldrich as Bill
Barrie Chase as Farida
Stanley Ralph Ross as Arab singer (voice; uncredited)

text: Production[edit]

text: This section needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (January 2017) (Learn how and when to remove this template message)

text: Locations[edit]

text: Principal photography started April 26, 1965, at the 20th Century-Fox Studios and 20th Century-Fox Ranch, California. Other filming locations, simulating the desert, were Buttercup Valley, Arizona and Pilot Knob Mesa, California. The flying sequences were all filmed at Pilot Knob Mesa near Winterhaven, located in California's Imperial Valley, on the western fringes of Yuma, Arizona.

text: Aircraft used[edit]

text: In 2005, Hollywood aviation historian Simon Beck identified the aircraft used in the film:

text:
Fairchild C-82A Packet, N6887C – flying shots.
Fairchild C-82A Packet, N4833V – outdoor location wreck.
Fairchild C-82A Packet, N53228 – indoor studio wreck.
Fairchild R4Q-1 Flying Boxcar (the USMC C-119C variant), BuNo. 126580 – non-flying Phoenix prop.
Tallmantz Phoenix P-1, N93082 – flying Phoenix aircraft.
North American O-47A, N4725V – second flying Phoenix.

text: The C-82As were from Steward-Davies Inc. at Long Beach, California, while the O-47A came from the Planes of Fame air museum in California. The R4Q-1 was purchased from Allied Aircraft of Phoenix, Arizona. The aerial camera platform was a B-25J Mitchell, N1042B, which was also used in the 1970 film Catch-22. The flying sequences were flown by Paul Mantz, co-owner of the Tallmantz Aviation, filling in for his partner Frank Tallman, who had injured his leg.

text: A famous racing/stunt/movie pilot and collector of warplanes, Paul Mantz was flying the Tallmantz Phoenix P-1, the machine that was "made of the wreckage", in front of the cameras on the morning of July 8, 1965. He was performing touch-and-go landings, and on one touchdown the fuselage buckled. The movie model broke apart and cartwheeled, killing Mantz and seriously injuring stuntman Bobby Rose on board.[5]

text: Although principal photography was completed on August 13, 1965, in order to complete filming, a North American O-47A (N4725V) from the Planes of Fame Air Museum in Chino, California was modified and used as a flying Phoenix stand-in. With the canopy removed, a set of skids attached to the main landing gear as well as ventral fin added to the tail, it sufficed as more-or-less a visual lookalike. Filming using the O-47A was completed in October/November 1965. It appears in the last flying scenes, painted to look like the earlier Phoenix P-1.

text: The final production utilized a mix of footage that included the O-47A, the "cobbled-together" Phoenix and Phoenix P-1.

text: The final credit on the screen was, "It should be remembered... that Paul Mantz, a fine man and a brilliant flyer gave his life in the making of this film..."

text: Reception[edit]

text: The film opened in selected theaters on December 15, 1965, with a full release in 1966. Bosley Crowther of the New York Times dismissed it as "grim and implausible",[6] while Variety praised the film as an "often-fascinating and superlative piece of filmmaking highlighted by standout performances and touches that show producer-director at his best."[7]

text: Awards[edit]

text: The Flight of the Phoenix was nominated for two Academy Awards: Ian Bannen for Supporting Actor and Michael Luciano for Film Editing.[8]