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 journalArticle

30 Citations (Scopus)

Abstract

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
Volume16
Issue number8
DOIs
StatePublished - Aug 1 2009

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Cell Extracts
Trinucleotide Repeats
DNA
Endonucleases
Huntington Disease
Proliferating Cell Nuclear Antigen
Nervous System Diseases

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Incision-dependent and error-free repair of (CAG)n/(CTG) n hairpins in human cell extracts. / Hou, Caixia; Chan, Nelson L.S.; Gu, Liya; Li, Guo Min.

In: Nature Structural and Molecular Biology, Vol. 16, No. 8, 01.08.2009, p. 869-875.

Research output: Contribution to journalArticle

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