title: A role for the arginine methylation of Rad9 in checkpoint control and cellular sensitivity to DNA damage.
abstract: The genome stability is maintained by coordinated action of DNA repairs and checkpoints, which delay progression through the cell cycle in response to DNA damage. Rad9 is conserved from yeast to human and functions in cell cycle checkpoint controls. Here, a regulatory mechanism for Rad9 function is reported. In this study Rad9 has been found to interact with and be methylated by protein arginine methyltransferase 5 (PRMT5). Arginine methylation of Rad9 plays a critical role in S/M and G2/M cell cycle checkpoints. The activation of the Rad9 downstream checkpoint effector Chk1 is impaired in cells only expressing a mutant Rad9 that cannot be methylated. Additionally, Rad9 methylation is also required for cellular resistance to DNA damaging stresses. In summary, we uncovered that arginine methylation is important for regulation of Rad9 function, and thus is a major element for maintaining genome integrity.
authors.affiliation: National Laboratory of Biomacromolecules and Center for Computational and Systems Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Ma
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhao
authors.forename: Junkang
authors.initials: J
authors.lastname: Qiu
authors.forename: Haiying
authors.initials: H
authors.lastname: Hang
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D000071877:Checkpoint Kinase 1; D004249:DNA Damage; D057809:HEK293 Cells; D006801:Humans; D008745:Methylation; D051379:Mice; D009154:Mutation; D011494:Protein Kinases / Q000378:metabolism; D011496:Protein Methyltransferases / Q000378:metabolism; D011484:Protein-Arginine N-Methyltransferases
chemical_list: D018797:Cell Cycle Proteins; C069930:rad9 protein; D001120:Arginine; D011496:Protein Methyltransferases; C400529:PRMT5 protein, human; D011484:Protein-Arginine N-Methyltransferases; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; C000605869:Chek1 protein, mouse