DNA damage tolerance, mismatch repair and genome instability

Bioessays. 1994 Nov;16(11):833-9. doi: 10.1002/bies.950161110.


DNA mismatch repair is an important pathway of mutation avoidance. It also contributes to the cytotoxic effects of some kinds of DNA damage, and cells defective in mismatch repair are resistant, or tolerant, to the presence of some normally cytotoxic base analogues in their DNA. The absence of a particular mismatch binding function from some mammalian cells confers resistance to the base analogues O6-methylguanine and 6-thioguanine in DNA. Cells also acquire a spontaneous mutator phenotype as a consequence of this defect. Impaired mismatch binding can cause an instability in DNA microsatellite regions that comprise repeated dinucleotides. Microsatellite DNA instability is common in familial and sporadic colon carcinomas as well as in a number of other tumours. Several independent lines of investigation have identified defects in mismatch repair proteins that are causally related to these cancers.

Publication types

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

MeSH terms

  • Animals
  • Bacterial Proteins / physiology
  • Base Sequence
  • CHO Cells
  • Colonic Neoplasms / chemically induced
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Cricetinae
  • DNA Damage*
  • DNA Repair*
  • DNA, Satellite / genetics*
  • Escherichia coli / drug effects
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Female
  • Fungal Proteins / physiology
  • Genome*
  • Guanine / analogs & derivatives
  • Guanine / chemistry
  • Humans
  • Male
  • Mammals / genetics
  • Methylation
  • Methyltransferases / physiology
  • Molecular Sequence Data
  • Neoplasms / genetics*
  • O(6)-Methylguanine-DNA Methyltransferase
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Sister Chromatid Exchange


  • Bacterial Proteins
  • DNA, Satellite
  • Fungal Proteins
  • Guanine
  • O-(6)-methylguanine
  • Methyltransferases
  • O(6)-Methylguanine-DNA Methyltransferase