Incision-dependent and error-free repair of (CAG)n/(CTG) n hairpins in human cell extracts

Caixia Hou, Nelson L.S. Chan, Liya Gu, Guo Min Li

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


Expansion of CAG/CTG trinucleotide repeats is associated with certain familial neurological disorders, including Huntington's disease. Increasing evidence suggests that formation of a stable DNA hairpin within CAG/CTG repeats during DNA metabolism contributes to their expansion. However, the molecular mechanism(s) by which cells remove CAG/CTG hairpins remain unknown. Here we demonstrate that human cell extracts can catalyze error-free repair of CAG/CTG hairpins in a nick-directed manner. The repair system specifically targets CAG/CTG tracts for incisions in the nicked DNA strand, followed by DNA resynthesis using the continuous strand as a template, thereby ensuring CAG/CTG stability. Proliferating cell nuclear antigen (PCNA) is required for the incision step of the hairpin removal, which uses distinct endonuclease activities for individual CAG/CTG hairpins depending on their strand locations and/or secondary structures. We discuss the implications of these data for understanding the etiology of neurological diseases and trinucleotide repeat instability.

Original languageEnglish (US)
Pages (from-to)869-875
Number of pages7
JournalNature Structural and Molecular Biology
Issue number8
StatePublished - Aug 2009

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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