Intrinsic apurinic/apyrimidinic (AP) endonuclease activity enables Bacillus subtilis DNA polymerase X to recognize, incise, and further repair abasic sites

摘要

The N-glycosidic bond can be hydrolyzed spontaneously or by glycosylases during removal of damaged bases by the base excision repair pathway, leading to the formation of highly mutagenic apurinic/apyrimidinic (AP) sites. Organisms encode for evolution-arily conserved repair machinery, including specific AP endonu-cleases that cleave the DNA backbone 5' to the AP site to prime further DNA repair synthesis. We report on the DNA polymerase X from the bacterium Bacillus subtilis (PolX_(Bs)) that, along with polymerization and 3'- 5' -exonuclease activities, possesses an intrinsic AP-endonucleaseactivity..Both, AP-endonucleaseand 3'-5'-exonu-clease activities are genetically linked and governed by the same metal ligands located at the C-terminal polymerase and histidinol phosphatase domain of the polymerase. The different catalytic functions of PolX_(Bs) enable it to perform recognition and incision at an AP site and further restoration (repair) of the original nucleo-tide in a standalone AP-endonuclease-independent way.