The interaction of DNA mismatch repair proteins with human exonuclease I

J Biol Chem. 2001 Aug 31;276(35):33011-8. doi: 10.1074/jbc.M102670200. Epub 2001 Jun 26.

Abstract

Exonucleolytic degradation of DNA is an essential part of many DNA metabolic processes including DNA mismatch repair (MMR) and recombination. Human exonuclease I (hExoI) is a member of a family of conserved 5' --> 3' exonucleases, which are implicated in these processes by genetic studies. Here, we demonstrate that hExoI binds strongly to hMLH1, and we describe interaction regions between hExoI and the MMR proteins hMSH2, hMSH3, and hMLH1. In addition, hExoI forms an immunoprecipitable complex with hMLH1/hPMS2 in vivo. The study of interaction regions suggests a biochemical mechanism of the involvement of hExoI as a downstream effector in MMR and/or DNA recombination.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Base Pair Mismatch*
  • Binding Sites
  • Carrier Proteins
  • Cloning, Molecular
  • DNA Repair Enzymes
  • DNA Repair*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Exodeoxyribonucleases / chemistry
  • Exodeoxyribonucleases / genetics
  • Exodeoxyribonucleases / metabolism*
  • Humans
  • Multidrug Resistance-Associated Proteins*
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • MutS Homolog 3 Protein
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Nuclear Proteins
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Sequence Deletion
  • Substrate Specificity

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • DNA-Binding Proteins
  • MLH1 protein, human
  • MSH3 protein, human
  • Multidrug Resistance-Associated Proteins
  • MutS Homolog 3 Protein
  • Neoplasm Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Recombinant Fusion Proteins
  • EXO1 protein, human
  • Exodeoxyribonucleases
  • exodeoxyribonuclease I
  • MSH2 protein, human
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • DNA Repair Enzymes
  • multidrug resistance-associated protein 1