TY - JOUR
T1 - A polycomb group protein, PHF1, is involved in the response to DNA double-strand breaks in human cell
AU - Hong, Zehui
AU - Jiang, Jie
AU - Lan, Li
AU - Nakajima, Satoshi
AU - Kanno, Shin Ichiro
AU - Koseki, Haruhiko
AU - Yasui, Akira
N1 - Funding Information:
We thank Drs Maria Jasin and Hiroshi Tauchi for providing us with expression vector pCMV3nls-I-SceI and HeLa cell line containing a stably integrated copy of recombination reporter vector SCneo. This work was supported in part by a grant from the Genome Network Project, a Grant-in-Aid for Scientific Research (A), 16201010, and Priority Areas Cancer, 18012003 from the Ministry of Education, Culture, Sports, Science and Technology, Japan (to A.Y.). Funding to pay the Open Access publication charges for this article was provided by the Genome Network Projects.
PY - 2008/5
Y1 - 2008/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=44349103099&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=44349103099&partnerID=8YFLogxK
U2 - 10.1093/nar/gkn146
DO - 10.1093/nar/gkn146
M3 - Article
C2 - 18385154
AN - SCOPUS:44349103099
VL - 36
SP - 2939
EP - 2947
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 9
ER -