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 purines ...

deoxyribonucleosides, deoxyadenosine and deoxyguanosine, and

ribonucleoside A ribonucleoside is a type of nucleoside including ribose as a component. One example of a ribonucleoside is cytidine Cytidine (symbol C or Cyd) is a nucleoside molecule that is formed when cytosine is attached to a ribose ring (also known as ...

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 building ...

guanosine Guanosine (symbol G or Guo) is a purine nucleoside comprising guanine attached to a ribose ( ribofuranose) ring via a β-N9- glycosidic bond. Guanosine can be phosphorylated to become guanosine monophosphate (GMP), cyclic guanosine monophosphate ...

, in which the β-N-

glycosidic bond A glycosidic bond or glycosidic linkage is a type of covalent 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 ...

is hydrolytically cleaved releasing a nucleic base,

adenine Adenine () ( symbol A or Ade) is a nucleobase (a purine derivative). It is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The three others are guanine, cytosine and thymine. Its deriv ...

guanine Guanine () ( symbol G or Gua) is one of the four main nucleobases 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 is ...

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

, respectively. More complex compounds containing nucleoside residues,

nucleotide Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecu ...

s and

nucleic acid Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main ...

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 othe ...

bases (

cytosine Cytosine () ( symbol C or Cyt) is one of the four nucleobases 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 attached ( ...

and

thymine Thymine () ( symbol T or Thy) is one of the four nucleobases 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 pyrimidin ...

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

When depurination occurs with DNA, 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 Base excision repair (BER) is a cellular mechanism, studied in the fields of biochemistry and genetics, that repairs damaged DNA throughout the cell cycle. It is responsible primarily for removing small, non-helix-distorting base lesions from ...

(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, m ...

, 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 specimens. Due to degradation processes (including cross-linking, deamination and fragmentation) ancient DNA is more degraded in comparison with contemporary genetic material. Even under the bes ...

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 rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) ...

Chemistry of the reaction

Depurination is not uncommon because purine is a good

leaving group In chemistry, a leaving group is defined by the IUPAC as an atom or group of atoms that detaches from the main or residual part of a substrate during a reaction or elementary step of a reaction. However, in common usage, the term is often limited ...

via the 9N-nitrogen (see the structure of a

). Furthermore, the

anomeric carbon In carbohydrate chemistry, a pair of anomers () is a pair of near-identical stereoisomers that differ at only the anomeric carbon, the carbon that bears the aldehyde or ketone functional group in the sugar's open-chain form. However, in order fo ...

is especially reactive towards

nucleophilic substitution In chemistry, a nucleophilic substitution is a class of chemical reactions in which an electron-rich chemical species (known as a nucleophile) replaces a functional group within another electron-deficient molecule (known as the electrophile). The ...

(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 Synthesis or synthesize may refer to: Science Chemistry and biochemistry * Chemical synthesis, the execution of chemical reactions to form a more complex molecule from chemical precursors **Organic synthesis, the chemical synthesis of organ ...

oligonucleotide Oligonucleotides are short DNA or RNA molecules, oligomers, that have a wide range of applications in genetic testing, research, and forensics. Commonly made in the laboratory by solid-phase chemical synthesis, these small bits of nucleic acids ...

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

References

* * *{{cite book , last1 = Alberts , first1 = Bruce , authorlink = Bruce Alberts , last2 = Johnson , first2 = Alexander , last3 = Lewis , first3 = Julian , last4 = Raff , first4 = Martin , last5 = Roberts , first5 = Keith , last6 = Walter , first6 = Peter , authorlink6 = Peter Walter , year = 2002 , title = Molecular Biology of the Cell , publisher = Garland Science , location = New York, NY , edition = 4th , isbn = 978-0-8153-3218-3 , oclc = 48122761 , url = https://books.google.com/books?id=hTLSRQAACAAJ , lccn = 2001054471 DNA Molecular genetics Mutation