Base Excision Repair

Base excision repair (BER) is the primary pathway for repairing small, non-helix-distorting base lesions — deaminated bases, oxidized bases, and alkylated bases — that arise spontaneously from metabolic byproducts and environmental agents. It is the most frequent DNA repair event in the cell, handling tens of thousands of lesions per day in a typical mammalian cell.

The mechanism is elegant in its simplicity: a DNA glycosylase recognizes the damaged base and cleaves the N-glycosidic bond, leaving an abasic site. An apurinic/apyrimidinic (AP) endonuclease nicks the DNA backbone at the abasic site, and a repair polymerase replaces the missing nucleotide. A DNA ligase seals the nick. The entire process can involve as few as one nucleotide (short-patch BER) or up to several nucleotides (long-patch BER).

BER handles the constant low-level damage that every cell experiences. It is the molecular equivalent of maintenance: not dramatic, not newsworthy, but without it the genome would erode from the accumulated wear of ordinary metabolism. The cell's most remarkable feature is not that it can repair catastrophic damage. It is that it never stops repairing trivial damage.