title: p38γ regulates UV-induced checkpoint signaling and repair of UV-induced DNA damage.
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.
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 N. Torrey Pines Road., La Jolla, CA 92037, USA.
authors.forename: Chia-Cheng
authors.initials: CC
authors.lastname: Wu
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Wu
authors.forename: Jiahuai
authors.initials: J
authors.lastname: Han
authors.forename: Peiqing
authors.initials: P
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D004249:DNA Damage; D004260:DNA Repair; D004789:Enzyme Activation; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D017353:Gene Deletion; D006657:Histones / Q000378:metabolism; D051379:Mice; D048291:Mitogen-Activated Protein Kinase 12 / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D016196:S Phase; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D018797:Cell Cycle Proteins; D006657:Histones; D016159:Tumor Suppressor Protein p53; D048291:Mitogen-Activated Protein Kinase 12