Repeat instability as the basis for human diseases and as a potential target for therapy

Nat Rev Mol Cell Biol. 2010 Mar;11(3):165-70. doi: 10.1038/nrm2854.


Expansions of repetitive DNA sequences cause numerous human neurological and neuromuscular diseases. Ongoing repeat expansions in patients can exacerbate disease progression and severity. As pathogenesis is connected to repeat length, a potential therapeutic avenue is to modulate disease by manipulating repeat expansion size--targeting DNA, the root-cause of symptoms. How repeat instability is mediated by DNA replication, repair, recombination, transcription and epigenetics may explain its contribution to pathogenesis and give insights into therapeutic strategies to block expansions or induce contractions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Base Sequence
  • DNA Damage / drug effects
  • DNA Repair / drug effects
  • DNA Replication / drug effects
  • Drug Therapy / methods
  • Genetic Predisposition to Disease / genetics*
  • Genomic Instability / drug effects
  • Genomic Instability / genetics*
  • Humans
  • Mice
  • Models, Biological
  • Transcription, Genetic / drug effects
  • Trinucleotide Repeat Expansion / genetics*
  • Trinucleotide Repeats / genetics*