In molecular genetics, depurination is an alteration of DNA in which the purine base (adenine or guanine) is removed from the deoxyribose sugar by hydrolysis of the beta-N-glycosidic link between them. After depurination, an apurinic site is formed where the sugar phosphate backbone remains and the sugar ring has a hydroxyl (-OH) group in the place of the purine. Studies estimate that as many as 5,000 purines are lost this way each day in a typical human cell.[1] One of the main causes of depurination is the presence of endogenous metabolites in cell undergoing chemical reactions. Depurinated bases 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, 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.[2] Loss of pyrimidine bases (Cytosine and Thymine) occurs by a similar mechanism, but at a substantially lower rate.
Hydrolytic depurination is one of the principal forms of damage to ancient DNA 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.
Depurination is not uncommon because purine is a good leaving group via the 8N-nitrogen (see the structure of a purine). 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.