New insights into the genetic instability in CCTG repeats

FEBS Lett. 2015 Oct 7;589(20 Pt B):3058-63. doi: 10.1016/j.febslet.2015.09.007. Epub 2015 Sep 16.


Tetranucleotide CCTG repeat expansion is associated with myotonic dystrophy type 2, which is an inherited and progressive muscle degeneration disease. Yet, no cure is available and the molecular mechanism of repeat expansion remains elusive. In this study, we used high-resolution nuclear magnetic resonance spectroscopy to reveal a mini-dumbbell structure formed by two CCTG repeats. Upon slippage in the nascent strand during DNA replication, the formation of the mini-dumbbell provides a possible pathway for a two-repeat expansion. In addition, fast exchange between two competing mini-dumbbells among three repeats results in a mini-loop structure that accounts for one-repeat expansion. These mini-dumbbell and mini-loop intermediates can also co-exist at multiple sites in CCTG repeats, leading to three or larger size repeat expansions.

Keywords: CCTG repeat expansion; DNA structure; Dumbbell; Myotonic dystrophy type 2; Nuclear magnetic resonance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • DNA / chemistry*
  • DNA / genetics
  • DNA Repeat Expansion
  • DNA Sequence, Unstable*
  • Humans
  • Magnetic Resonance Spectroscopy / methods
  • Models, Molecular
  • Myotonic Dystrophy / genetics
  • Nucleic Acid Conformation*
  • Repetitive Sequences, Nucleic Acid*


  • DNA