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

Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7166-9. doi: 10.1073/pnas.94.14.7166.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • DNA Polymerase I / genetics*
  • DNA Polymerase I / metabolism
  • DNA Repair*
  • DNA-(Apurinic or Apyrimidinic Site) Lyase
  • Deoxyribonuclease IV (Phage T4-Induced)
  • Humans
  • Lyases / genetics*
  • Lyases / metabolism
  • Plasmids
  • Saccharomyces cerevisiae

Substances

  • DNA Polymerase I
  • Deoxyribonuclease IV (Phage T4-Induced)
  • Lyases
  • DNA-(Apurinic or Apyrimidinic Site) Lyase