title: Interaction of human apurinic endonuclease and DNA polymerase beta in the base excision repair pathway.
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.
authors.affiliation: Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Bennett
authors.forename: D M
authors.initials: DM
authors.lastname: Wilson
authors.forename: D
authors.initials: D
authors.lastname: Wong
authors.forename: B
authors.initials: B
authors.lastname: Demple
mesh_terms: D004256:DNA Polymerase I / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D043223:Deoxyribonuclease IV (Phage T4-Induced); D006801:Humans; D008190:Lyases / Q000235:genetics* / Q000378:metabolism; D010957:Plasmids; D012441:Saccharomyces cerevisiae
chemical_list: D004256:DNA Polymerase I; D043223:Deoxyribonuclease IV (Phage T4-Induced); D008190:Lyases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase