DNA base damage recognition and processing

In living cells DNA base lesions are formed continuously as a consequence of normal metabolism and are also generated by a number of external factors. Simple base damages are repaired by base excision repair that is initiated by a damage specific DNA glycosylase, which removes the damaged base creating an abasic site (apurinic/apyrimidinic, AP site). AP endonuclease cleaves the phosphodiester bond 5′ to the AP site and then DNA polymerase β adds the first nucleotide to the 3′-end of the incised AP site and at the same time removes the 5′-sugar phosphate residue. DNA ligase completes the repair by sealing the DNA ends. These processes are directed and co-ordinated by multiple protein-protein interactions. This review focuses primarily on mammalian base excision repair, and in particular addresses the enzymology of the repair process and co-ordination of repair reactions. © 2005 Springer-Verlag Berlin Heidelberg.