Nathaniel C Holcomb

University of Kentucky, Lexington, Kentucky, United States

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Publications (1)4.57 Total impact

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    Lei Tian · Caixia Hou · Keli Tian · Nathaniel C Holcomb · Liya Gu · Guo-Min Li
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    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.
    Preview · Article · Jul 2009 · Journal of Biological Chemistry