A carboxy terminal domain of the hMSH-2 gene product is sufficient for binding specific mismatched oligonucleotides

Biochem Biophys Res Commun. 1996 Aug 5;225(1):289-95. doi: 10.1006/bbrc.1996.1168.

Abstract

The human MSH-2 gene product is a member of a highly conserved family of proteins which are involved in post-replication mismatch repair. hMSH-2 is homologous to Escherichia coli (E. coli) MutS and Sacchromyces cerevisiae MSH-1 and MSH-2 proteins, which recognise heteroduplex DNA at the sites of all single base mismatches and deletions or insertions up to 4 base pairs. hMSH-2 is one of the hereditary non-polyposis colorectal cancer (HNPCC) tumor suppressor genes, and maps to human chromosome 2p16. Alterations in the coding region of the hMSH-2 gene result in a mutator phenotype with marked instability of microsatellite sequences, indicative of a deficiency in DNA repair. It has been shown that purified hMSH-2 binds specifically to nucleotide mismatches in double-stranded DNA. Here we demonstrate that a region of high homology between the members of this class of proteins contains a type A nucleotide binding site consensus sequence which has ATPase activity and is sufficient to bind DNA containing specific mismatched residues.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Amino Acid Sequence
  • Bacterial Proteins / metabolism
  • Base Sequence
  • Binding Sites
  • Cloning, Molecular
  • Conserved Sequence
  • DNA / chemistry
  • DNA / metabolism*
  • DNA Primers
  • DNA Repair
  • DNA-Binding Proteins / metabolism
  • Escherichia coli / metabolism
  • Escherichia coli Proteins*
  • Fungal Proteins / metabolism
  • Humans
  • Mitochondrial Proteins
  • Molecular Sequence Data
  • MutS DNA Mismatch-Binding Protein
  • MutS Homolog 2 Protein
  • Oligodeoxyribonucleotides / chemistry
  • Oligodeoxyribonucleotides / metabolism*
  • Oligopeptides
  • Peptides / chemistry
  • Peptides / metabolism
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / metabolism*
  • Recombinant Fusion Proteins / isolation & purification
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins*
  • Sequence Homology, Amino Acid

Substances

  • Bacterial Proteins
  • DNA Primers
  • DNA-Binding Proteins
  • Escherichia coli Proteins
  • Fungal Proteins
  • MSH1 protein, S cerevisiae
  • Mitochondrial Proteins
  • Oligodeoxyribonucleotides
  • Oligopeptides
  • Peptides
  • Proto-Oncogene Proteins
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • DNA
  • FLAG peptide
  • Adenosine Triphosphatases
  • MSH2 protein, S cerevisiae
  • MSH2 protein, human
  • MutS DNA Mismatch-Binding Protein
  • MutS Homolog 2 Protein
  • MutS protein, E coli