INTERACTION OF HUMAN APURINIC ENDONUCLEASE AND DNA-POLYMERASE-BETA INTHE BASE EXCISION-REPAIR PATHWAY

Mutagenic abasic (AP) sites are generated directly by DNA-damaging age nts or by DNA glycosylases acting in base excision repair. AP sites ar e corrected via incision by AP endonucleases, removal of deoxyribose 5 -phosphate, repair synthesis, and ligation. Mammalian DNA polymerase b eta (Pol beta) carries out most base excision repair synthesis and als o can excise deoxyribose 5-phosphate after AP endonuclease incision. Y east two-hybrid analysis now indicates protein-protein contact between Pol beta and human AP endonuclease (Ape protein). In vitro, binding o f Ape protein to uncleaved AP sites loads Pol beta into a ternary comp lex with Ape and the AP-DNA. After incision by Ape, only Pol beta exhi bits stable DNA binding. Kinetic experiments indicated that Ape accele rates the excision of 5'-terminal deoxyribose 5-phosphate by Pol beta. Thus, the two central players of the base excision repair pathway are coordinated in sequential reactions.