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http://dx.doi.org/10.5483/BMBRep.2011.44.5.352

Knock-down of human MutY homolog (hMYH) decreases phosphorylation of checkpoint kinase 1 (Chk1) induced by hydroxyurea and UV treatment  

Hahm, Soo-Hyun (Department of Advanced Technology Fusion, Konkuk University)
Park, Jong-Hwa (Department of Genetic Engineering and Graduate School of Biotechnology, Kyung Hee University)
Ko, Sung-Il (Department of Advanced Technology Fusion, Konkuk University)
Lee, You-Ri (Department of Advanced Technology Fusion, Konkuk University)
Chung, In-Sik (Department of Genetic Engineering and Graduate School of Biotechnology, Kyung Hee University)
Chung, Ji-Hyung (Yonsei Integrative Research Institute for Cerebral & Cardiovascular Diseases (YIRIC), Yonsei University Health System)
Kang, Lin-Woo (Department of Advanced Technology Fusion, Konkuk University)
Han, Ye-Sun (Department of Advanced Technology Fusion, Konkuk University)
Publication Information
BMB Reports / v.44, no.5, 2011 , pp. 352-357 More about this Journal
Abstract
The effect of human MutY homolog (hMYH) on the activation of checkpoint proteins in response to hydroxyurea (HU) and ultraviolet (UV) treatment was investigated in hMYH-disrupted HEK293 cells. hMYH-disrupted cells decreased the phosphorylation of Chk1 upon HU or UV treatment and increased the phosphorylation of Cdk2 and the amount of Cdc25A, but not Cdc25C. In siMYH-transfected cells, the increased rate of phosphorylated Chk1 upon HU or UV treatment was lower than that in siGFP-transfected cells, meaning that hMYH was involved in the activation mechanism of Chk1 upon DNA damage. The phosphorylation of ataxia telangiectasia and Rad3-related protein (ATR) upon HU or UV treatment was decreased in hMYH-disrupted HEK293 and HaCaT cells. Co-immunoprecipitation experiments showed that hMYH was immunoprecipitated by anti-ATR. These results suggest that hMYH may interact with ATR and function as a mediator of Chk1 phosphorylation in response to DNA damage.
Keywords
Ataxia telangiectasia and Rad3-related protein (ATR); Checkpoint kinase 1 (Chk1); Human MutY homolog (hMYH); Hydroxyurea (HU); Ultraviolet (UV);
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