depurinate

Depurination is the hydrolytic loss of purine nucleobases—adenine and guanine—from DNA, resulting from cleavage of the N-glycosidic bond that links the base to the deoxyribose sugar. The reaction produces an abasic site (an AP site) in the DNA strand, where no base is present to pair with the opposite strand. Depurination is one of the most common forms of spontaneous DNA damage in cells, with the rate influenced by factors such as temperature, pH, and local DNA sequence context.

The chemical process begins with hydrolysis of the glycosidic bond, which removes the purine base but leaves the sugar-phosphate backbone intact. AP sites are unstable and can lead to strand breaks or incorrect nucleotides being incorporated during replication if not repaired promptly. Although depurination itself does not insert mutations, the presence of AP sites increases the risk of mutagenesis and genomic instability during DNA replication and repair.

Repair of depurinated DNA occurs primarily through the base excision repair (BER) pathway. An AP endonuclease recognizes the AP site and cleaves the DNA backbone adjacent to the abasic site, creating a single-strand break with a suitable terminus. A DNA polymerase then fills the gap by inserting the correct nucleotide, and a DNA ligase seals the nick, restoring the DNA sequence. In bacteria and eukaryotes, homologous enzymes perform these steps, though the specific proteins differ between organisms.

Depurination is a fundamental aspect of DNA damage and informs studies of mutation rates, aging, and cellular responses to stress. It is considered alongside other forms of spontaneous and induced DNA damage in discussions of genomic maintenance and DNA repair.