The dual nature of mismatch repair as antimutator and mutator: for better or for worse

Sara Thornby Bak, Despoina Sakellariou, Javier Pena-Diaz*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

DNA is constantly under attack by a number of both exogenous and endogenous agents that challenge its integrity. Among the mechanisms that have evolved to counteract this deleterious action, mismatch repair (MMR) has specialized in removing DNA biosynthetic errors that occur when replicating the genome. Malfunction or inactivation of this system results in an increase in spontaneous mutability and a strong predisposition to tumor development. Besides this key corrective role, MMR proteins are involved in other pathways of DNA metabolism such as mitotic and meiotic recombination and processing of oxidative damage. Surprisingly, MMR is also required for certain mutagenic processes. The mutagenic MMR has beneficial consequences contributing to the generation of a vast repertoire of antibodies through class switch recombination and somatic hypermutation processes. However, this non-canonical mutagenic MMR also has detrimental effects; it promotes repeat expansions associated with neuromuscular and neurodegenerative diseases and may contribute to cancer/disease-related aberrant mutations and translocations. The reaction responsible for replication error correction has been the most thoroughly studied and it is the subject to numerous reviews. This review describes briefly the biochemistry of MMR and focuses primarily on the non-canonical MMR activities described in mammals as well as emerging research implicating interplay of MMR and chromatin.

Original languageEnglish
Article number287
JournalFrontiers in Genetics
Volume5
Number of pages12
ISSN1664-8021
DOIs
Publication statusPublished - 21. Aug 2014
Externally publishedYes

Keywords

  • Antibody diversification
  • Chromatin modifiers
  • Class switch recombination
  • Neurodegenerative diseases
  • Non-canonical mismatch repair
  • Somatic hypermutation
  • Trinucleotide repeats

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