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DOI QR Code

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)
  • 투고 : 2010.12.18
  • 심사 : 2011.03.15
  • 발행 : 2011.05.31

초록

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.

키워드

참고문헌

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피인용 문헌

  1. A physical association between the human mutY homolog (hMYH) and DNA topoisomerase II-binding protein 1 (hTopBP1) regulates Chk1-induced cell cycle arrest in HEK293 cells vol.5, pp.1, 2015, https://doi.org/10.1186/s13578-015-0042-x
  2. Mammalian MutY homolog (MYH or MUTYH) protects cells from oxidative DNA damage vol.13, 2014, https://doi.org/10.1016/j.dnarep.2013.10.011
  3. Silencing of human DNA polymerase   causes replication stress and is synthetically lethal with an impaired S phase checkpoint vol.41, pp.1, 2013, https://doi.org/10.1093/nar/gks1016
  4. MutY DNA Glycosylase Protects Cells From Tumor Necrosis Factor Alpha-Induced Necroptosis vol.118, pp.7, 2017, https://doi.org/10.1002/jcb.25866
  5. Cancer-associated variants and a common polymorphism of MUTYH exhibit reduced repair of oxidative DNA damage using a GFP-based assay in mammalian cells vol.33, pp.11, 2012, https://doi.org/10.1093/carcin/bgs270
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  9. Oral ingestion of silver nanoparticles induces genomic instability and DNA damage in multiple tissues vol.9, pp.2, 2015, https://doi.org/10.3109/17435390.2014.902520
  10. Exposure to Engineered Nanomaterials: Impact on DNA Repair Pathways vol.18, pp.7, 2017, https://doi.org/10.3390/ijms18071515
  11. Human MutY homolog induces apoptosis in etoposide-treated HEK293 cells vol.4, pp.6, 2012, https://doi.org/10.3892/ol.2012.921