Interaction of human apurinic endonuclease and DNA polymerase beta in the base excision repair pathway.
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.
Bennett
R A
RA
Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, MA 02115, USA.
Wilson
D M
DM
Wong
D
D
Demple
B
B
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
D004256:DNA Polymerase I; D043223:Deoxyribonuclease IV (Phage T4-Induced); D008190:Lyases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase