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Nucleic Acids Research Advance Access originally published online on April 1, 2008
Nucleic Acids Research 2008 36(9):2939-2947; doi:10.1093/nar/gkn146
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Nucleic Acids Research, 2008, Vol. 36, No. 9 2939-2947
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Molecular Biology

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

Zehui Hong1, Jie Jiang1, Li Lan1, Satoshi Nakajima1, Shin-ichiro Kanno1, Haruhiko Koseki2 and Akira Yasui1,*

1Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University, Seiryomachi 4-1, Aobaku, Sendai 980-8575 and 2Laboratory of Developmental Genetics, Riken Research Center for Allergy and Immunology, Suehiro-cho 1-7-22, Tsurumi-ku, Yokohama 230-0045, Japan

*To whom correspondence should be addressed. Tel: +81 22 717 8465; Fax: +81 22 717 8470; Email: ayasui{at}idac.tohoku.ac.jp

Received December 18, 2007. Revised March 4, 2008. Accepted March 17, 2008.

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.


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Z. Hong, J. Jiang, K. Hashiguchi, M. Hoshi, L. Lan, and A. Yasui
Recruitment of mismatch repair proteins to the site of DNA damage in human cells
J. Cell Sci., October 1, 2008; 121(19): 3146 - 3154.
[Abstract] [Full Text] [PDF]



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