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p38γ regulates UV-induced checkpoint signaling
and repair of UV-induced DNA damage |
| Chia-Cheng Wu1,Xiaohua Wu2,Jiahuai Han3,Peiqing Sun4, |
| 1.Department of Immunology
and Microbial Science, The Scripps Research Institute, 10550 N. Torrey
Pines Road., La Jolla, CA 92037, USA; 2.Department of Molecular
and Experimental Medicine, The Scripps Research Institute, 10550 N.
Torrey Pines Road., La Jolla, CA 92037, USA; 3.Department of Immunology
and Microbial Science, The Scripps Research Institute, 10550 N. Torrey
Pines Road., La Jolla, CA 92037, USA；Key Laboratory of Ministry
of Education for Cell Biology and Tumor Cell Engineering, School of
Life Sciences, Xiamen University, Xiamen 361005, China; 4.Dempartment of Molecular
Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road.,
La Jolla, CA 92037, USA; |
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Abstract In eukaryotic cells, DNA damage triggers activation of checkpoint signaling pathways that coordinate cell cycle arrest and repair of damaged DNA. These DNA damage responses serve to maintain genome stability and prevent accumulation of genetic mutations and development of cancer. The p38 MAPK was previously implicated in cellular responses to several types of DNA damage. However, the role of each of the four p38 isoforms and the mechanism for their involvement in DNA damage responses remained poorly understood. In this study, we demonstrate that p38γ, but not the other p38 isoforms, contributes to the survival of UV-treated cells. Deletion of p38γ sensitizes cells to UV exposure, accompanied by prolonged S phase cell cycle arrest and increased rate of apoptosis. Further investigation reveal that p38γ is essential for the optimal activation of the checkpoint signaling caused by UV, and for the efficient repair of UV-induced DNA damage. These findings have established a novel role of p38γ in UV-induced DNA damage responses, and suggested that p38γ contributes to the ability of cells to cope with UV exposure by regulating the checkpoint signaling pathways and the repair of damaged DNA.
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| Keywords
p38γ
DNA damage
UV
DNA repair
checkpoint signaling
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Issue Date: 01 June 2010
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