Isolation of an hMSH2-p160 heterodimer that restores DNA mismatch repair to tumor cells

Science. 1995 Jun 30;268(5219):1909-12. doi: 10.1126/science.7604264.

Abstract

A mismatch-binding heterodimer of hMSH2 and a 160-kilodalton polypeptide has been isolated from HeLa cells by virtue of its ability to restore mismatch repair to nuclear extracts of hMSH2-deficient LoVo colorectal tumor cells. This heterodimer, designated hMutS alpha, also restores mismatch repair to extracts of alkylation-tolerant MT1 lymphoblastoid cells and HCT-15 colorectal tumor cells, which are selectively defective in the repair of base-base and single-nucleotide insertion-deletion mismatches. Because HOT-15 cells appear to be free of hMSH2 mutations, this selective repair defect is likely a result of a deficiency of the hMutS alpha 160-kilodalton subunit, and mutations in the corresponding gene may confer hypermutability and cancer predisposition.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Base Composition
  • Base Sequence
  • Colorectal Neoplasms / chemistry
  • Colorectal Neoplasms / genetics*
  • DNA Damage
  • DNA Repair / genetics*
  • DNA, Neoplasm / metabolism*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / isolation & purification*
  • DNA-Binding Proteins / physiology
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Molecular Weight
  • Mutation
  • Nucleic Acid Heteroduplexes / metabolism
  • Sequence Deletion
  • Tumor Cells, Cultured

Substances

  • DNA, Neoplasm
  • DNA-Binding Proteins
  • G-T mismatch-binding protein
  • Nucleic Acid Heteroduplexes