Interaction of human apurinic endonuclease and DNA polymerase beta in the base excision repair pathway.

Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, MA 02115, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 08/1997; 94(14):7166-9. DOI: 10.1073/pnas.94.14.7166
Source: PubMed

ABSTRACT Mutagenic abasic (AP) sites are generated directly by DNA-damaging agents or by DNA glycosylases acting in base excision repair. AP sites are corrected via incision by AP endonucleases, removal of deoxyribose 5-phosphate, repair synthesis, and ligation. Mammalian DNA polymerase beta (Polbeta) carries out most base excision repair synthesis and also can excise deoxyribose 5-phosphate after AP endonuclease incision. Yeast two-hybrid analysis now indicates protein-protein contact between Polbeta and human AP endonuclease (Ape protein). In vitro, binding of Ape protein to uncleaved AP sites loads Polbeta into a ternary complex with Ape and the AP-DNA. After incision by Ape, only Polbeta exhibits stable DNA binding. Kinetic experiments indicated that Ape accelerates the excision of 5'-terminal deoxyribose 5-phosphate by Polbeta. Thus, the two central players of the base excision repair pathway are coordinated in sequential reactions.

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