Depurination is a chemical reaction of

purine Purine is a heterocyclic aromatic organic compound that consists of two rings (pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which include substituted puri ...

deoxyribonucleoside A deoxyribonucleotide is a nucleotide that contains deoxyribose. They are the monomeric units of the informational biopolymer, deoxyribonucleic acid (DNA). Each deoxyribonucleotide comprises three parts: a deoxyribose sugar (monosaccharide), a nitr ...

s, deoxyadenosine and deoxyguanosine, and ribonucleosides,

adenosine Adenosine (symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9- glycosidic bond. Adenosine is one of the four nucleoside build ...

or guanosine, in which the β-N-

glycosidic bond A glycosidic bond or glycosidic linkage is a type of ether bond that joins a carbohydrate (sugar) molecule to another group, which may or may not be another carbohydrate. A glycosidic bond is formed between the hemiacetal or hemiketal group o ...

is hydrolytically cleaved releasing a nucleic base,

adenine Adenine (, ) (nucleoside#List of nucleosides and corresponding nucleobases, symbol A or Ade) is a purine nucleotide base that is found in DNA, RNA, and Adenosine triphosphate, ATP. Usually a white crystalline subtance. The shape of adenine is ...

guanine Guanine () (symbol G or Gua) is one of the four main nucleotide bases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine ( uracil in RNA). In DNA, guanine is paired with cytosine. The guanine nucleoside ...

, respectively. The second product of depurination of deoxyribonucleosides and ribonucleosides is sugar, 2'-

deoxyribose Deoxyribose, or more precisely 2-deoxyribose, is a monosaccharide with idealized formula H−(C=O)−(CH2)−(CHOH)3−H. Its name indicates that it is a deoxy sugar, meaning that it is derived from the sugar ribose by loss of a hydroxy group. D ...

and

ribose Ribose is a simple sugar and carbohydrate with molecular formula C5H10O5 and the linear-form composition H−(C=O)−(CHOH)4−H. The naturally occurring form, , is a component of the ribonucleotides from which RNA is built, and so this comp ...

, respectively. More complex compounds containing nucleoside residues,

nucleotide Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...

s and

nucleic acid Nucleic acids are large biomolecules that are crucial in all cells and viruses. They are composed of nucleotides, which are the monomer components: a pentose, 5-carbon sugar, a phosphate group and a nitrogenous base. The two main classes of nuclei ...

s, also suffer from depurination. Deoxyribonucleosides and their derivatives are substantially more prone to depurination than their corresponding ribonucleoside counterparts. Loss of

pyrimidine Pyrimidine (; ) is an aromatic, heterocyclic, organic compound similar to pyridine (). One of the three diazines (six-membered heterocyclics with two nitrogen atoms in the ring), it has nitrogen atoms at positions 1 and 3 in the ring. The oth ...

bases (

cytosine Cytosine () (symbol C or Cyt) is one of the four nucleotide bases found in DNA and RNA, along with adenine, guanine, and thymine ( uracil in RNA). It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attac ...

and

thymine Thymine () (symbol T or Thy) is one of the four nucleotide bases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The others are adenine, guanine, and cytosine. Thymine is also known as 5-methyluracil, a pyrimidine ...

) occurs by a similar mechanism, but at a substantially lower rate. Apurinic Site

When depurination occurs with

DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

, it leads to the formation of apurinic site and results in an alteration of the structure. Studies estimate that as many as 5,000 purines are lost this way each day in a typical human cell. In cells, one of the main causes of depurination is the presence of endogenous metabolites undergoing chemical reactions. Apurinic sites in double-stranded DNA are efficiently repaired by portions of the base excision repair (BER) pathway. Depurinated bases in single-stranded DNA undergoing replication can lead to

mutations In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosi ...

, because in the absence of information from the complementary strand, BER can add an incorrect base at the apurinic site, resulting in either a transition or transversion mutation. Depurination is known to play a major role in cancer initiation. Hydrolytic depurination is one of the principal forms of damage to

ancient DNA Ancient DNA (aDNA) is DNA isolated from ancient sources (typically Biological specimen, specimens, but also environmental DNA). Due to degradation processes (including Crosslinking of DNA, cross-linking, deamination and DNA fragmentation, fragme ...

in fossil or subfossil material, since the base remains unrepaired. This results in both loss of information (the base sequence), and difficulties in recovery and ''in vitro'' replication of the damaged molecule by the

polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to make millions to billions of copies of a specific DNA sample rapidly, allowing scientists to amplify a very small sample of DNA (or a part of it) sufficiently to enable detailed st ...

Chemistry of the reaction

Depurination is not uncommon because purine is a good leaving group via the 9N-nitrogen (see the structure of a

). Furthermore, the anomeric carbon is especially reactive towards nucleophilic substitution (effectively making the carbon-oxygen bond shorter, stronger and more polar, while making the carbon-purine bond longer and weaker). This makes the bond especially susceptible to hydrolysis. In chemical synthesis of

oligonucleotide Oligonucleotides are short DNA or RNA molecules, oligomers, that have a wide range of applications in genetic testing, Recombinant DNA, research, and Forensic DNA, forensics. Commonly made in the laboratory by Oligonucleotide synthesis, solid-phase ...

s, depurination is one of the major factors limiting the length of synthetic oligonucleotides.

References

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