A polycomb group protein, PHF1, is involved in the response to DNA double-strand breaks in human cell.
A polycomb group protein, PHF1, is involved in the response to DNA double-strand breaks in human cell.
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DOI：
10.1093/nar/gkn146
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发表时间：
2008-05
影响因子：
14.9
通讯作者：
Yasui A
中科院分区：
文献类型：
--
作者：
Hong Z;Jiang J;Lan L;Nakajima S;Kanno S;Koseki H;Yasui A
DNA双链断裂（DSB）是由内源性和外源性遗传毒性胁迫引起的最具毒性的DNA损伤，并且已知通过同源重组或非同源末端连接过程来修复。虽然许多蛋白质已被确定参与这两个过程中的任何一个，但整个过程仍然难以捉摸。Polycomb group（PcG）蛋白是表观遗传染色质修饰剂，参与基因沉默、癌症发展以及胚胎和成体干细胞的维持。通过筛选响应于DNA损伤的蛋白质，我们发现，PHF 1，果蝇polycomb-like，Pcl，蛋白质的人类同源物，被招募到DSB照射后立即和10分钟内解离。在DSB的积累是Ku 70/Ku 80依赖性的，和PHF 1的敲低导致X射线敏感性，并增加HeLa细胞中同源重组的频率。我们发现PHF 1与Ku 70/Ku 80物理相互作用，表明PHF 1促进非同源末端连接过程。此外，我们发现PHF 1与许多参与DNA损伤反应的蛋白质（RAD 50、SMC 1、DHX 9和p53）相互作用，进一步表明PHF 1除了在PcG中的功能外，还参与基因组维持过程。
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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DOI：
10.1083/jcb.200510130
发表时间：
2006-04-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bekker-Jensen S;Lukas C;Kitagawa R;Melander F;Kastan MB;Bartek J;Lukas J
通讯作者：
Lukas J
DOI：
10.1084/jem.20020851
发表时间：
2002-08-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Difilippantonio MJ;Petersen S;Chen HT;Johnson R;Jasin M;Kanaar R;Ried T;Nussenzweig A
通讯作者：
Nussenzweig A
影响因子：
3.8
作者：
Gorski, MM;Romeijn, RJ;Pastink, A
通讯作者：
Pastink, A
影响因子：
4.8
作者：
Kim, JS;Krasieva, TB;Yokomori, K
通讯作者：
Yokomori, K
影响因子：
56.9
作者：
Lee, JH;Paull, TT
通讯作者：
Paull, TT