Intrinsic apurinic/apyrimidinic (AP) endonuclease activity enables Bacillus subtilis DNA polymerase X to recognize, incise, and further repair abasic sites

Proc Natl Acad Sci U S A. 2010 Nov 9;107(45):19219-24. doi: 10.1073/pnas.1013603107. Epub 2010 Oct 25.

Abstract

The N-glycosidic bond can be hydrolyzed spontaneously or by glycosylases during removal of damaged bases by the base excision repair pathway, leading to the formation of highly mutagenic apurinic/apyrimidinic (AP) sites. Organisms encode for evolutionarily conserved repair machinery, including specific AP endonucleases that cleave the DNA backbone 5' to the AP site to prime further DNA repair synthesis. We report on the DNA polymerase X from the bacterium Bacillus subtilis (PolX(Bs)) that, along with polymerization and 3'-5'-exonuclease activities, possesses an intrinsic AP-endonuclease activity. Both, AP-endonuclease and 3'-5'-exonuclease activities are genetically linked and governed by the same metal ligands located at the C-terminal polymerase and histidinol phosphatase domain of the polymerase. The different catalytic functions of PolX(Bs) enable it to perform recognition and incision at an AP site and further restoration (repair) of the original nucleotide in a standalone AP-endonuclease-independent way.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacillus subtilis / enzymology*
  • Catalysis
  • DNA Repair*
  • DNA-(Apurinic or Apyrimidinic Site) Lyase / metabolism*
  • DNA-Directed DNA Polymerase / genetics*

Substances

  • DNA polymerase X
  • DNA-Directed DNA Polymerase
  • DNA-(Apurinic or Apyrimidinic Site) Lyase