DNA triplet repeat expansion and mismatch repair

Ravi R. Iyer, Anna Pluciennik, Marek Napierala, Robert D. Wells

Research output: Contribution to journalReview articlepeer-review

82 Scopus citations


DNA mismatch repair is a conserved antimutagenic pathway that maintains genomic stability through rectification of DNA replication errors and attenuation of chromosomal rearrangements. Paradoxically, mutagenic action of mismatch repair has been implicated as a cause of triplet repeat expansions that cause neurological diseases such as Huntington disease and myotonic dystrophy. This mutagenic process requires the mismatch recognition factor MutSβ and the MutLα (and/or possibly MutLγ) endonuclease, and is thought to be triggered by the transient formation of unusual DNA structures within the expanded triplet repeat element. This review summarizes the current knowledge of DNA mismatch repair involvement in triplet repeat expansion, which encompasses in vitro biochemical findings, cellular studies, and various in vivo transgenic animal model experiments. We present current mechanistic hypotheses regarding mismatch repair protein function in mediating triplet repeat expansions and discuss potential therapeutic approaches targeting the mismatch repair pathway.

Original languageEnglish (US)
Pages (from-to)199-226
Number of pages28
JournalAnnual review of biochemistry
StatePublished - Jun 2 2015
Externally publishedYes


  • DNA mismatch repair
  • Hereditary neurological diseases
  • Non-B-DNA structures
  • Repeat expansion diseases
  • Triplet repeats

ASJC Scopus subject areas

  • Biochemistry


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