Molecular mechanism of base excision repair of uracil-containing DNA in yeast cell-free extracts

J Biol Chem. 1997 Sep 19;272(38):24064-71. doi: 10.1074/jbc.272.38.24064.

Abstract

Base excision repair (BER) constitutes a ubiquitous excision repair mechanism, which is responsible for the removal of multiple types of damaged and inappropriate bases in DNA. We have employed a yeast cell-free system to examine the biochemical mechanism of the BER pathway in lower eukaryotes. Using uracil-containing DNA as a model substrate, we demonstrate that yeast BER requires Apn1 protein, an Escherichia coli endonuclease IV homolog. In extracts of an apn1 deletion mutant, the 5'-incision at AP (apurinic/apyrimidinic) sites is not detectable, supporting the notion that yeast contains only one major 5'-AP endonuclease. The processing of the 5'-deoxyribose phosphate moieties was found to be a rate-limiting step. During BER of uracil-containing DNA, repair patch sizes of 1-5 nucleotides were detected, with single nucleotide repair patches predominant.

Publication types

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

MeSH terms

  • Cell-Free System
  • DNA Repair Enzymes
  • DNA Repair*
  • DNA, Fungal / chemistry
  • DNA, Fungal / genetics*
  • Endodeoxyribonucleases / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins*
  • Uracil / chemistry*

Substances

  • DNA, Fungal
  • Saccharomyces cerevisiae Proteins
  • Uracil
  • Endodeoxyribonucleases
  • Apn1 protein, S cerevisiae
  • DNA Repair Enzymes