Mismatch recognition protein MutS_@b does not hijack (CAG)n hairpin repair in vitro

Lei Tian, Caixia Hou, Keli Tian, Nathaniel C. Holcomb, Liya Gu, Guo Min Li

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

CAG repeats form stable hairpin structures, which are believed to be responsible for CAG repeat expansions associated with certain human neurological diseases. Human cells possess an accurate DNA hairpin repair system that prevents expansion of disease-associated CAG repeats. Based on transgenic animal studies, it is suggested that (CAG)n expansion is caused by abnormal binding of the MutSβ mismatch recognition protein to (CAG)n hairpins, leading to hijacking mismatch repair function during (CAG)n hairpin repair. We demonstrate here that MutSβ displays identical biochemical and biophysical activities (including ATP-provoked conformational change, ATPase, ATP binding, and ADP binding) when interacting with a (CAG)n hairpin and a mismatch. More importantly, our in vitro functional hairpin repair assays reveal that excess MutSβ does not inhibit (CAG)n hairpin repair in HeLa nuclear extracts. Evidence presented here provides a novel view as to whether or not MutSβ is involved in CAG repeat instability in humans.

Original languageEnglish (US)
Pages (from-to)20452-20456
Number of pages5
JournalJournal of Biological Chemistry
Volume284
Issue number31
DOIs
StatePublished - Jul 31 2009

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Repair
Adenosine Triphosphate
Genetically Modified Animals
Proteins
DNA Mismatch Repair
DNA Repair
Adenosine Diphosphate
Adenosine Triphosphatases
Assays
Animals
Cells
In Vitro Techniques
DNA

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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Mismatch recognition protein MutS_@b does not hijack (CAG)n hairpin repair in vitro. / Tian, Lei; Hou, Caixia; Tian, Keli; Holcomb, Nathaniel C.; Gu, Liya; Li, Guo Min.

In: Journal of Biological Chemistry, Vol. 284, No. 31, 31.07.2009, p. 20452-20456.

Research output: Contribution to journalArticle

Tian, Lei ; Hou, Caixia ; Tian, Keli ; Holcomb, Nathaniel C. ; Gu, Liya ; Li, Guo Min. / Mismatch recognition protein MutS_@b does not hijack (CAG)n hairpin repair in vitro. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 31. pp. 20452-20456.
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