- Volume 44 Issue 5
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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)
- Received : 2010.12.18
- Accepted : 2011.03.15
- Published : 2011.05.31
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.
Ataxia telangiectasia and Rad3-related protein (ATR);Checkpoint kinase 1 (Chk1);Human MutY homolog (hMYH);Hydroxyurea (HU);Ultraviolet (UV)
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