DNA mismatch repair: molecular mechanism, cancer, and ageing

Mech Ageing Dev. Jul-Aug 2008;129(7-8):391-407. doi: 10.1016/j.mad.2008.02.012. Epub 2008 Mar 4.

Abstract

DNA mismatch repair (MMR) proteins are ubiquitous players in a diverse array of important cellular functions. In its role in post-replication repair, MMR safeguards the genome correcting base mispairs arising as a result of replication errors. Loss of MMR results in greatly increased rates of spontaneous mutation in organisms ranging from bacteria to humans. Mutations in MMR genes cause hereditary nonpolyposis colorectal cancer, and loss of MMR is associated with a significant fraction of sporadic cancers. Given its prominence in mutation avoidance and its ability to target a range of DNA lesions, MMR has been under investigation in studies of ageing mechanisms. This review summarizes what is known about the molecular details of the MMR pathway and the role of MMR proteins in cancer susceptibility and ageing.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Aging / genetics*
  • Animals
  • DNA Mismatch Repair*
  • DNA Repair Enzymes / chemistry*
  • DNA Repair Enzymes / genetics
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / genetics
  • Humans
  • Mice
  • Mutation
  • Neoplasms / genetics*

Substances

  • DNA-Binding Proteins
  • DNA Repair Enzymes