title: A polycomb group protein, PHF1, is involved in the response to DNA double-strand breaks in human cell.
abstract: DNA double-strand breaks (DSBs) represent the most toxic DNA damage arisen from endogenous and exogenous genotoxic stresses and are known to be repaired by either homologous recombination or nonhomologous end-joining processes. Although many proteins have been identified to participate in either of the processes, the whole processes still remain elusive. Polycomb group (PcG) proteins are epigenetic chromatin modifiers involved in gene silencing, cancer development and the maintenance of embryonic and adult stem cells. By screening proteins responding to DNA damage using laser micro-irradiation, we found that PHF1, a human homolog of Drosophila polycomb-like, Pcl, protein, was recruited to DSBs immediately after irradiation and dissociated within 10 min. The accumulation at DSBs is Ku70/Ku80-dependent, and knockdown of PHF1 leads to X-ray sensitivity and increases the frequency of homologous recombination in HeLa cell. We found that PHF1 interacts physically with Ku70/Ku80, suggesting that PHF1 promotes nonhomologous end-joining processes. Furthermore, we found that PHF1 interacts with a number of proteins involved in DNA damage responses, RAD50, SMC1, DHX9 and p53, further suggesting that PHF1, besides the function in PcG, is involved in genome maintenance processes.
authors.affiliation: Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University, Seiryomachi 4-1, Aobaku, Sendai 980-8575, Japan.
authors.forename: Zehui
authors.initials: Z
authors.lastname: Hong
authors.forename: Jie
authors.initials: J
authors.lastname: Jiang
authors.forename: Li
authors.initials: L
authors.lastname: Lan
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nakajima
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Kanno
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Koseki
authors.forename: Akira
authors.initials: A
authors.lastname: Yasui
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D002460:Cell Line; D006224:Cricetinae; D004247:DNA / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D000072200:Ku Autoantigen; D007834:Lasers; D063146:Polycomb-Group Proteins; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D011995:Recombination, Genetic; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; C112309:PHF1 protein, human; D063146:Polycomb-Group Proteins; D014157:Transcription Factors; D004247:DNA; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen