A polycomb group protein, PHF1, is involved in the response to DNA double-strand breaks in human cell

Zehui Hong, Jie Jiang, Li Lan, Satoshi Nakajima, Shin Ichiro Kanno, Haruhiko Koseki, Akira Yasui

研究成果: Article査読

76 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)2939-2947
ページ数9
ジャーナルNucleic acids research
36
9
DOI
出版ステータスPublished - 2008 5月

ASJC Scopus subject areas

  • 遺伝学

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