hMSH2 forms specific mispair-binding complexes with hMSH3 and hMSH6

Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13629-34. doi: 10.1073/pnas.93.24.13629.

Abstract

The genetic and biochemical properties of three human MutS homologues, hMSH2, hMSH3, and hMSH6, have been examined. The full-length hMSH6 cDNA and genomic locus were isolated and characterized, and it was demonstrated that the hMSH6 gene consisted of 10 exons and mapped to chromosome 2p15-16. The hMSH3 cDNA was in some cases found to contain a 27-bp deletion resulting in a loss of nine amino acids, depending on the individual from which the cDNA was isolated. hMSH2, hMSH3, and hMSH6 all showed similar tissue-specific expression patterns. hMSH2 protein formed a complex with both hMSH3 and hMSH6 proteins, similar to protein complexes demonstrated by studies of the Saccharomyces cerevisiae MSH2, MSH3, and MSH6. hMSH2 was also found to form a homomultimer complex, but neither hMSH3 nor hMSH6 appear to interact with themselves or each other. Analysis of the mismatched nucleotide-binding specificity of the hMSH2-hMSH3 and hMSH2-hMSH6 protein complexes showed that they have overlapping but not identical binding specificity. These results help to explain the distribution of mutations in different mismatch-repair genes seen in hereditary nonpolyposis colon cancer.

Publication types

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

MeSH terms

  • Base Sequence
  • Binding Sites
  • Chromosome Mapping
  • Chromosomes, Human, Pair 2*
  • Cloning, Molecular
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics
  • DNA Primers
  • DNA Repair
  • DNA, Complementary
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • Exons
  • Fungal Proteins / metabolism*
  • Gene Library
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • MutS Homolog 2 Protein
  • MutS Homolog 3 Protein
  • Oligodeoxyribonucleotides
  • Protein Binding
  • Protein Biosynthesis
  • RNA, Messenger / metabolism
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins*
  • Sequence Deletion
  • Substrate Specificity
  • Transcription, Genetic

Substances

  • DNA Primers
  • DNA, Complementary
  • DNA-Binding Proteins
  • Fungal Proteins
  • MSH3 protein, S cerevisiae
  • MSH6 protein, S cerevisiae
  • MutS Homolog 3 Protein
  • Oligodeoxyribonucleotides
  • RNA, Messenger
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • MSH2 protein, S cerevisiae
  • MutS Homolog 2 Protein

Associated data

  • GENBANK/U54777
  • GENBANK/U73732
  • GENBANK/U73733
  • GENBANK/U73734
  • GENBANK/U73735
  • GENBANK/U73736
  • GENBANK/U73737