Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development and reproduction of all known organisms and many viruses. DNA and ribonucleic acid are nucleic acids; the two DNA strands are known as polynucleotides as they are composed of simpler monomeric units called nucleotides. Each nucleotide is composed of one of four nitrogen-containing nucleobases, a sugar called deoxyribose, a phosphate group; the nucleotides are joined to one another in a chain by covalent bonds between the sugar of one nucleotide and the phosphate of the next, resulting in an alternating sugar-phosphate backbone. The nitrogenous bases of the two separate polynucleotide strands are bound together, according to base pairing rules, with hydrogen bonds to make double-stranded DNA; the complementary nitrogenous bases are divided into two groups and purines. In DNA, the pyrimidines are cytosine. Both strands of double-stranded DNA store the same biological information.
This information is replicated as and when the two strands separate. A large part of DNA is non-coding, meaning that these sections do not serve as patterns for protein sequences; the two strands of DNA are thus antiparallel. Attached to each sugar is one of four types of nucleobases, it is the sequence of these four nucleobases along the backbone. RNA strands are created using DNA strands as a template in a process called transcription. Under the genetic code, these RNA strands specify the sequence of amino acids within proteins in a process called translation. Within eukaryotic cells, DNA is organized into long structures called chromosomes. Before typical cell division, these chromosomes are duplicated in the process of DNA replication, providing a complete set of chromosomes for each daughter cell. Eukaryotic organisms store most of their DNA inside the cell nucleus as nuclear DNA, some in the mitochondria as mitochondrial DNA, or in chloroplasts as chloroplast DNA. In contrast, prokaryotes store their DNA only in circular chromosomes.
Within eukaryotic chromosomes, chromatin proteins, such as histones and organize DNA. These compacting structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed. DNA was first isolated by Friedrich Miescher in 1869, its molecular structure was first identified by Francis Crick and James Watson at the Cavendish Laboratory within the University of Cambridge in 1953, whose model-building efforts were guided by X-ray diffraction data acquired by Raymond Gosling, a post-graduate student of Rosalind Franklin. DNA is used by researchers as a molecular tool to explore physical laws and theories, such as the ergodic theorem and the theory of elasticity; the unique material properties of DNA have made it an attractive molecule for material scientists and engineers interested in micro- and nano-fabrication. Among notable advances in this field are DNA origami and DNA-based hybrid materials. DNA is a long polymer made from repeating units called nucleotides.
The structure of DNA is dynamic along its length, being capable of coiling into tight loops and other shapes. In all species it is composed of two helical chains, bound to each other by hydrogen bonds. Both chains are coiled around the same axis, have the same pitch of 34 angstroms; the pair of chains has a radius of 10 angstroms. According to another study, when measured in a different solution, the DNA chain measured 22 to 26 angstroms wide, one nucleotide unit measured 3.3 Å long. Although each individual nucleotide is small, a DNA polymer can be large and contain hundreds of millions, such as in chromosome 1. Chromosome 1 is the largest human chromosome with 220 million base pairs, would be 85 mm long if straightened. DNA does not exist as a single strand, but instead as a pair of strands that are held together; these two long strands coil in the shape of a double helix. The nucleotide contains both a segment of the backbone of a nucleobase. A nucleobase linked to a sugar is called a nucleoside, a base linked to a sugar and to one or more phosphate groups is called a nucleotide.
A biopolymer comprising multiple linked nucleotides is called a polynucleotide. The backbone of the DNA strand is made from alternating sugar residues; the sugar in DNA is 2-deoxyribose, a pentose 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 are known as the 3′-end, 5′-end carbons, the prime symbol being used to distinguish these carbon atoms from those of the base to which the deoxyribose forms a glycosidic bond. When imagining DNA, each phosphoryl is considered to "belong" to the nucleotide whose 5′ carbon forms a bond therewith. Any DNA strand therefore has one end at which there is a phosphoryl attached to the 5′ carbon of a ribose and another end a
A nitrogenous base, or nitrogen-containing base, is an organic molecule with a nitrogen atom that has the chemical properties of a base. The main biological function of a nitrogenous base is to bond nucleic acids together. A nitrogenous base owes its basic properties to the lone pair of electrons of a nitrogen atom. Nitrogenous bases are classified as the derivatives of two parent compounds and purine, they are due to their aromaticity, planar. Both pyrimidines and purines resemble pyridine and are thus weak bases and unreactive towards electrophilic aromatic substitution. In the biological sciences, nitrogenous bases are termed nucleobases because of their role in nucleic acids - their flat shape is important when considering their roles as the building blocks of DNA and RNA. A set of five nitrogenous bases is used in the construction of nucleotides, which in turn build up nucleic acids like DNA and RNA; these nitrogenous bases are adenine, guanine and cytosine. Thymine and uracil are distinguished by the presence or absence of a methyl group on the fifth carbon of these heterocyclic six-membered rings.
The nitrogenous bases form hydrogen bonds between opposing DNA strands to form the rungs of the "twisted ladder" or double helix of DNA or a biological catalyst, found in the nucleotides. Adenine is always paired with thymine, guanine is always paired with cytosine; these are known as base pairs. Adenine forms two hydrogen bonds with thymine in DNA and two hydrogen bonds with uracil in RNA, while three hydrogen bonds are formed between guanine and cytosine. There are a variety of other non-canonical base pairs that occur in nature due to the versatility of these molecular structures. Uracil is only present in RNA, replacing thymine. Pyrimidines include thymine and uracil, they have a single ring structure. Purines include guanine, they have a double ring structure
Nucleobases known as nitrogenous bases or simply bases, are nitrogen-containing biological compounds that form nucleosides, which in turn are components of nucleotides, with all of these monomers constituting the basic building blocks of nucleic acids. The ability of nucleobases to form base pairs and to stack one upon another leads directly to long-chain helical structures such as ribonucleic acid and deoxyribonucleic acid. Five nucleobases—adenine, guanine and uracil —are called primary or canonical, they function as the fundamental units of the genetic code, with the bases A, G, C, T being found in DNA while A, G, C, U are found in RNA. Thymine and uracil are identical excepting. Adenine and guanine have a fused-ring skeletal structure derived of purine, hence they are called purine bases; the simple-ring structure of cytosine and thymine is derived of pyrimidine, so those three bases are called the pyrimidine bases. Each of the base pairs in a typical double-helix DNA comprises a purine and a pyrimidine: either an A paired with a T or a C paired with a G.
These purine-pyrimidine pairs, which are called base complements, connect the two strands of the helix and are compared to the rungs of a ladder. The pairing of purines and pyrimidines may result, in part, from dimensional constraints, as this combination enables a geometry of constant width for the DNA spiral helix; the A-T and C-G pairings function to form double or triple hydrogen bonds between the amine and carbonyl groups on the complementary bases. In August 2011, a report based on NASA studies of meteorites suggested that nucleobases such as adenine, xanthine, purine, 2,6-diaminopurine, 6,8-diaminopurine may have formed in outer space as well as on earth; the origin of the term base reflects these compounds' chemical properties in acid-base reactions, but those properties are not important for understanding most of the biological functions of nucleobases. At the sides of nucleic acid structure, phosphate molecules successively connect the two sugar-rings of two adjacent nucleotide monomers, thereby creating a long chain biomolecule.
These chain-joins of phosphates with sugars create the "backbone" strands for a single- or double helix biomolecule. In the double helix of DNA, the two strands are oriented chemically in opposite directions, which permits base pairing by providing complementarity between the two bases, and, essential for replication of or transcription of the encoded information found in DNA. DNA and RNA contain other bases that have been modified after the nucleic acid chain has been formed. In DNA, the most common modified base is 5-methylcytosine. In RNA, there are many modified bases, including those contained in the nucleosides pseudouridine, inosine, 7-methylguanosine. Hypoxanthine and xanthine are two of the many bases created through mutagen presence, both of them through deamination. Hypoxanthine is produced from adenine, xanthine from guanine, uracil results from deamination of cytosine; these are examples of modified guanosine. These are examples of modified thymine or uridine. A vast number of nucleobase analogues exist.
The most common applications are used as fluorescent probes, either directly or indirectly, such as aminoallyl nucleotide, which are used to label cRNA or cDNA in microarrays. Several groups are working on alternative "extra" base pairs to extend the genetic code, such as isoguanine and isocytosine or the fluorescent 2-amino-6-purine and pyrrole-2-carbaldehyde. In medicine, several nucleoside analogues are used as antiviral agents; the viral polymerase incorporates these compounds with non-canonical bases. These compounds are activated in the cells by being converted into nucleotides. At least one set of new base pairs has been announced as of May 2014. Nucleoside Nucleotide Nucleic acid notation Nucleic acid sequence Base pairing in DNA Double Helix
A base pair is a unit consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA and RNA. Dictated by specific hydrogen bonding patterns, Watson–Crick base pairs allow the DNA helix to maintain a regular helical structure, subtly dependent on its nucleotide sequence; the complementary nature of this based-paired structure provides a redundant copy of the genetic information encoded within each strand of DNA. The regular structure and data redundancy provided by the DNA double helix make DNA well suited to the storage of genetic information, while base-pairing between DNA and incoming nucleotides provides the mechanism through which DNA polymerase replicates DNA and RNA polymerase transcribes DNA into RNA. Many DNA-binding proteins can recognize specific base-pairing patterns that identify particular regulatory regions of genes. Intramolecular base pairs can occur within single-stranded nucleic acids.
This is important in RNA molecules, where Watson–Crick base pairs permit the formation of short double-stranded helices, a wide variety of non-Watson–Crick interactions allow RNAs to fold into a vast range of specific three-dimensional structures. In addition, base-pairing between transfer RNA and messenger RNA forms the basis for the molecular recognition events that result in the nucleotide sequence of mRNA becoming translated into the amino acid sequence of proteins via the genetic code; the size of an individual gene or an organism's entire genome is measured in base pairs because DNA is double-stranded. Hence, the number of total base pairs is equal to the number of nucleotides in one of the strands; the haploid human genome is estimated to be about 3.2 billion bases long and to contain 20,000–25,000 distinct protein-coding genes. A kilobase is a unit of measurement in molecular biology equal to 1000 base pairs of DNA or RNA; the total amount of related DNA base pairs on Earth is estimated at 5.0×1037 and weighs 50 billion tonnes.
In comparison, the total mass of the biosphere has been estimated to be as much as 4 TtC. Hydrogen bonding is the chemical interaction. Appropriate geometrical correspondence of hydrogen bond donors and acceptors allows only the "right" pairs to form stably. DNA with high GC-content is more stable than DNA with low GC-content. But, contrary to popular belief, the hydrogen bonds do not stabilize the DNA significantly; the larger nucleobases and guanine, are members of a class of double-ringed chemical structures called purines. Purines are complementary only with pyrimidines: pyrimidine-pyrimidine pairings are energetically unfavorable because the molecules are too far apart for hydrogen bonding to be established. Purine-pyrimidine base-pairing of AT or GC or UA results in proper duplex structure; the only other purine-pyrimidine pairings would be AC and GT and UG. The GU pairing, with two hydrogen bonds, does occur often in RNA. Paired DNA and RNA molecules are comparatively stable at room temperature, but the two nucleotide strands will separate above a melting point, determined by the length of the molecules, the extent of mispairing, the GC content.
Higher GC content results in higher melting temperatures. On the converse, regions of a genome that need to separate — for example, the promoter regions for often-transcribed genes — are comparatively GC-poor. GC content and melting temperature must be taken into account when designing primers for PCR reactions; the following DNA sequences illustrate pair double-stranded patterns. By convention, the top strand is written from the 5' end to the 3' end. A base-paired DNA sequence: ATCGATTGAGCTCTAGCG TAGCTAACTCGAGATCGCThe corresponding RNA sequence, in which uracil is substituted for thymine in the RNA strand: AUCGAUUGAGCUCUAGCG UAGCUAACUCGAGAUCGC Chemical analogs of nucleotides can take the place of proper nucleotides and establish non-canonical base-pairing, leading to errors in DNA replication and DNA transcription; this is due to their isosteric chemistry. One common mutagenic base analog is 5-bromouracil, which resembles thymine but can base-pair to guanine in its enol form. Other chemicals, known as DNA intercalators, fit into the gap between adjacent bases on a single strand and induce frameshift mutations by "masquerading" as a base, causing the DNA replication machinery to skip or insert additional nucleotides at the intercalated site.
Most intercalators are known or suspected carcinogens. Examples include ethidium acridine. An unnatural base pair is a designed subunit of DNA, created in a laboratory and does not occur in nature. DNA sequences have been described which use newly created nucleobases to form a third base pair, in addition to the two ba
Nucleic acids are the biopolymers, or small biomolecules, essential to all known forms of life. The term nucleic acid is the overall name for DNA and RNA, they are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. If the sugar is a compound ribose, the polymer is RNA. Nucleic acids are the most important of all biomolecules, they are found in abundance in all living things, where they function to create and encode and store information in the nucleus of every living cell of every life-form organism on Earth. In turn, they function to transmit and express that information inside and outside the cell nucleus—to the interior operations of the cell and to the next generation of each living organism; the encoded information is contained and conveyed via the nucleic acid sequence, which provides the'ladder-step' ordering of nucleotides within the molecules of RNA and DNA. Strings of nucleotides are bonded to form helical backbones—typically, one for RNA, two for DNA—and assembled into chains of base-pairs selected from the five primary, or canonical, which are: adenine, guanine and uracil.
Using amino acids and the process known as protein synthesis, the specific sequencing in DNA of these nucleobase-pairs enables storing and transmitting coded instructions as genes. In RNA, base-pair sequencing provides for manufacturing new proteins that determine the frames and parts and most chemical processes of all life forms. Nuclein were discovered by Friedrich Miescher in 1869. In the early 1880s Albrecht Kossel further purifies the substance and discovers its acidic properties, he also identifies the nucleobases. In 1889 Richard Altmann creates the term nucleic acid In 1938 Astbury and Bell published the first X-ray diffraction pattern of DNA. In 1953 Watson and Crick determined the structure of DNA. Experimental studies of nucleic acids constitute a major part of modern biological and medical research, form a foundation for genome and forensic science, the biotechnology and pharmaceutical industries; the term nucleic acid is the overall name for DNA and RNA, members of a family of biopolymers, is synonymous with polynucleotide.
Nucleic acids were named for their initial discovery within the nucleus, for the presence of phosphate groups. Although first discovered within the nucleus of eukaryotic cells, nucleic acids are now known to be found in all life forms including within bacteria, mitochondria, chloroplasts and viroids.. All living cells contain both DNA and RNA, while viruses contain either DNA or RNA, but not both; the basic component of biological nucleic acids is the nucleotide, each of which contains a pentose sugar, a phosphate group, a nucleobase. Nucleic acids are generated within the laboratory, through the use of enzymes and by solid-phase chemical synthesis; the chemical methods enable the generation of altered nucleic acids that are not found in nature, for example peptide nucleic acids. Nucleic acids are very large molecules. Indeed, DNA molecules are the largest individual molecules known. Well-studied biological nucleic acid molecules range in size from 21 nucleotides to large chromosomes. In most cases occurring DNA molecules are double-stranded and RNA molecules are single-stranded.
There are numerous exceptions, however—some viruses have genomes made of double-stranded RNA and other viruses have single-stranded DNA genomes, and, in some circumstances, nucleic acid structures with three or four strands can form. Nucleic acids are linear polymers of nucleotides; each nucleotide consists of three components: a purine or pyrimidine nucleobase, a pentose sugar, a phosphate group. The substructure consisting of a nucleobase plus sugar is termed a nucleoside. Nucleic acid types differ in the structure of the sugar in their nucleotides–DNA contains 2'-deoxyribose while RNA contains ribose; the nucleobases found in the two nucleic acid types are different: adenine and guanine are found in both RNA and DNA, while thymine occurs in DNA and uracil occurs in RNA. The sugars and phosphates in nucleic acids are connected to each other in an alternating chain through phosphodiester linkages. In conventional nomenclature, the carbons to which the phosphate groups attach are the 3'-end and the 5'-end carbons of the sugar.
This gives nucleic acids directionality, the ends of nucleic acid molecules are referred to as 5'-end and 3'-end. The nucleobases are joined to the sugars via an N-glycosidic linkage involving a nucleobase ring nitrogen and the 1' carbon of the pentose sugar ring. Non-standard nucleosides are found in both RNA and DNA and arise from modification of the standard nucleosides within the DNA molecule or the primary RNA transcript. Transfer RNA molecules contain a large number of modified nucleosides. Double-stranded nucleic acids are made up of complementary sequences, in which extensive Watson-Crick base pairing results in a repeated and quite uniform double-helical three-dimensional structure. In contrast, single-stranded
In chemistry, a dehydration reaction is a conversion that involves the loss of water from the reacting molecule or ion. Dehydration reactions are the reverse of a hydration reaction. Common dehydrating agents used in organic synthesis include sulfuric alumina. Dehydration reactions are effected with heating; the classic example of a dehydration reaction is the Fischer esterification, which involves treating a carboxylic acid with an alcohol in the presence of a dehydrating agent: RCO2H + R′OH ⇌ RCO2R′ + H2OTwo monosaccharides, such as glucose and fructose, can be joined together using dehydration synthesis. The new molecule, consisting of two monosaccharides, is called a disaccharide; the process of hydrolysis is the reverse reaction, meaning that the water is recombined with the two hydroxyl groups and the disaccharide reverts to being monosaccharides. In the related condensation reaction water is released from two different reactants. In organic synthesis, there are many examples of dehydration reaction, for example dehydration of alcohols or sugars.
Other examples of dehydration synthesis reactions are the formation of triglycerides from fatty acids and the formation of glycosidic bonds between carbohydrate molecules, such as the formation of maltose from two glucose molecules. Hydration reaction
Nucleotides are organic molecules that serve as the monomer units for forming the nucleic acid polymers deoxyribonucleic acid and ribonucleic acid, both of which are essential biomolecules within all life-forms on Earth. Nucleotides are the building blocks of nucleic acids. A nucleoside is a 5-carbon sugar, thus a nucleoside plus a phosphate group yields a nucleotide. Nucleotides play a central role in metabolism at a fundamental, cellular level, they carry packets of chemical energy—in the form of the nucleoside triphosphates Adenosine triphosphate, Guanosine triphosphate, Cytidine triphosphate and Uridine triphosphate —throughout the cell to the many cellular functions that demand energy, which include: synthesizing amino acids and cell membranes and parts, moving the cell and moving cell parts, dividing the cell, etc. In addition, nucleotides participate in cell signaling, are incorporated into important cofactors of enzymatic reactions. In experimental biochemistry, nucleotides can be radiolabeled with radionuclides to yield radionucleotides.
A nucleotide is composed of three distinctive chemical sub-units: a five-carbon sugar molecule, a nitrogenous base—which two together are called a nucleoside—and one phosphate group. With all three joined, a nucleotide is termed a "nucleoside monophosphate"; the chemistry sources ACS Style Guide and IUPAC Gold Book prescribe that a nucleotide should contain only one phosphate group, but common usage in molecular biology textbooks extends the definition to include molecules with two, or with three, phosphates. Thus, the terms "nucleoside diphosphate" or "nucleoside triphosphate" may indicate nucleotides. Nucleotides contain either a purine or a pyrimidine base—i.e. The nitrogenous base molecule known as a nucleobase—and are termed ribonucleotides if the sugar is ribose, or deoxyribonucleotides if the sugar is deoxyribose. Individual phosphate molecules repetitively connect the sugar-ring molecules in two adjacent nucleotide monomers, thereby connecting the nucleotide monomers of a nucleic acid end-to-end into a long chain.
These chain-joins of sugar and phosphate molecules create a'backbone' strand for a single- or double helix. In any one strand, the chemical orientation of the chain-joins runs from the 5'-end to the 3'-end —referring to the five carbon sites on sugar molecules in adjacent nucleotides. In a double helix, the two strands are oriented in opposite directions, which permits base pairing and complementarity between the base-pairs, all, essential for replicating or transcribing the encoded information found in DNA. Unlike in nucleic acid nucleotides, singular cyclic nucleotides are formed when the phosphate group is bound twice to the same sugar molecule, i.e. at the corners of the sugar hydroxyl groups. These individual nucleotides function in cell metabolism rather than the nucleic acid structures of long-chain molecules. Nucleic acids are polymeric macromolecules assembled from nucleotides, the monomer-units of nucleic acids; the purine bases adenine and guanine and pyrimidine base cytosine occur in both DNA and RNA, while the pyrimidine bases thymine and uracil in just one.
Adenine forms a base pair with thymine with two hydrogen bonds, while guanine pairs with cytosine with three hydrogen bonds. Nucleotides can be synthesized by a variety of means both in vitro and in vivo. In vitro, protecting groups may be used during laboratory production of nucleotides. A purified nucleoside is protected to create a phosphoramidite, which can be used to obtain analogues not found in nature and/or to synthesize an oligonucleotide. In vivo, nucleotides can be recycled through salvage pathways; the components used in de novo nucleotide synthesis are derived from biosynthetic precursors of carbohydrate and amino acid metabolism, from ammonia and carbon dioxide. The liver is the major organ of de novo synthesis of all four nucleotides. De novo synthesis of pyrimidines and purines follows two different pathways. Pyrimidines are synthesized first from aspartate and carbamoyl-phosphate in the cytoplasm to the common precursor ring structure orotic acid, onto which a phosphorylated ribosyl unit is covalently linked.
Purines, are first synthesized from the sugar template onto which the ring synthesis occurs. For reference, the syntheses of the purine and pyrimidine nucleotides are carried out by several enzymes in the cytoplasm of the cell, not within a specific organelle. Nucleotides undergo breakdown such that useful parts can be reused in synthesis reactions to create new nucleotides; the synthesis of the pyrimidines CTP and UTP occurs in the cytoplasm and starts with the formation of carbamoyl phosphate from glutamine and CO2. Next, aspartate carbamoyltransferase catalyzes a condensation reaction between aspartate and carbamoyl phosphate to form carbamoyl aspartic acid, cyclized into 4,5-dihydroorotic acid by dihydroorotase; the latter is converted to orotate by dihydroorotate oxidase. The net reaction is: -Dihydroorotate + O2 → Orotate + H2O2Orotate is covalently linked with a phosphorylated ribosyl unit; the covalent linkage between the ribose and pyrimidine occurs at position C1 of the ribose unit, which contains a pyrophosphate, N1 of the pyrimidine ring.
Orotate phosphoribosyltransferase catalyzes the net reaction yielding orotidine monophosphate: Or