title: New insights into the genetic instability in CCTG repeats.
abstract: 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.
authors.affiliation: Department of Chemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
authors.forename: Pei
authors.initials: P
authors.lastname: Guo
authors.affiliation: Department of Chemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong. Electronic address: lams@cuhk.edu.hk.
authors.forename: Sik Lok
authors.initials: SL
authors.lastname: Lam
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D042622:DNA Repeat Expansion; D043243:DNA Sequence, Unstable; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D009223:Myotonic Dystrophy / Q000235:genetics; D009690:Nucleic Acid Conformation; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D004247:DNA
keywords: CCTG repeat expansion; DNA structure; Dumbbell; Myotonic dystrophy type 2; Nuclear magnetic resonance