Structure-forming repeats and their impact on genome stability

Curr Opin Genet Dev. 2021 Apr;67:41-51. doi: 10.1016/j.gde.2020.10.006. Epub 2020 Dec 3.


Repetitive sequences throughout the genome are a major source of endogenous DNA damage, due to the propensity of many of them to form alternative non-B DNA structures that can interfere with replication, transcription, and DNA repair. These repetitive sequences are prone to breakage (fragility) and instability (changes in repeat number). Repeat fragility and expansions are linked to several diseases, including many cancers and neurodegenerative diseases, hence the importance of understanding the mechanisms that cause genome instability and contribute to these diseases. This review focuses on recent findings of mechanisms causing repeat fragility and instability, new associations between repeat expansions and genetic diseases, and potential therapeutic options to target repeat expansions.

Publication types

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

MeSH terms

  • DNA / genetics
  • DNA / ultrastructure*
  • DNA Damage / genetics
  • DNA Repair / genetics
  • DNA Replication / genetics
  • Genome / genetics*
  • Genomic Instability / genetics
  • Humans
  • Nucleic Acid Conformation
  • Repetitive Sequences, Nucleic Acid / genetics*
  • Transcription, Genetic*


  • DNA