Cohesin promotes the repair of ionizing radiation-induced DNA double-strand breaks in replicated chromatin.
Cohesin promotes the repair of ionizing radiation-induced DNA double-strand breaks in replicated chromatin.
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粘着蛋白可促进复制染色质中电离辐射诱导的DNA双链断裂的修复。
DOI：
10.1093/nar/gkp976
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发表时间：
2010-01
影响因子：
14.9
通讯作者：
Rothkamm K
中科院分区：
文献类型：
--
作者：
Bauerschmidt C;Arrichiello C;Burdak-Rothkamm S;Woodcock M;Hill MA;Stevens DL;Rothkamm K
在有丝分裂之前，内聚蛋白复合体在合成后将姐妹染色单体保持在一起。它还有助于酵母和高等真核生物中的复制后DNA修复，并在人类细胞中的激光诱导损伤部位积累。我们的目标是确定在细胞周期的G2期X射线照射的人类细胞中，粘附素亚基SMC 1和Rad 21是否有助于DNA双链断裂修复。RNA干扰介导的SMC 1耗竭使HeLa细胞对X射线敏感。通过γ H2 AX/53 BP 1灶分析测量的辐射诱导的DNA双链断裂的修复在G2中在SMC 1或Rad 21缺失的细胞中比在对照中慢，但在G1中不慢。抑制DNA损伤激酶DNA-PK，而不是ATM，进一步抑制了G2中的粘着蛋白耗尽细胞中的病灶丢失。SMC 1缺失对G1或晚S/G2期DNA单链断裂修复没有影响。Rad 21和SMC 1被招募到G2期细胞中X射线诱导的DNA损伤的位点，但不在G1期，并且仅当DNA损伤集中在部分屏蔽的超软X射线产生的亚核条纹中时。我们的研究结果表明，cohesin复合物有助于细胞存活，通过促进修复辐射诱导的DNA双链断裂在G2期细胞中的ATM依赖性途径。
The cohesin protein complex holds sister chromatids together after synthesis until mitosis. It also contributes to post-replicative DNA repair in yeast and higher eukaryotes and accumulates at sites of laser-induced damage in human cells. Our goal was to determine whether the cohesin subunits SMC1 and Rad21 contribute to DNA double-strand break repair in X-irradiated human cells in the G2 phase of the cell cycle. RNA interference-mediated depletion of SMC1 sensitized HeLa cells to X-rays. Repair of radiation-induced DNA double-strand breaks, measured by γH2AX/53BP1 foci analysis, was slower in SMC1- or Rad21-depleted cells than in controls in G2 but not in G1. Inhibition of the DNA damage kinase DNA-PK, but not ATM, further inhibited foci loss in cohesin-depleted cells in G2. SMC1 depletion had no effect on DNA single-strand break repair in either G1 or late S/G2. Rad21 and SMC1 were recruited to sites of X-ray-induced DNA damage in G2-phase cells, but not in G1, and only when DNA damage was concentrated in subnuclear stripes, generated by partially shielded ultrasoft X-rays. Our results suggest that the cohesin complex contributes to cell survival by promoting the repair of radiation-induced DNA double-strand breaks in G2-phase cells in an ATM-dependent pathway.
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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
影响因子：
16
作者：
Haering, CH;Löwe, J;Nasmyth, K
通讯作者：
Nasmyth, K
影响因子：
4.8
作者：
Kim, JS;Krasieva, TB;Yokomori, K
通讯作者：
Yokomori, K
影响因子：
8
作者：
Burdak-Rothkamm, S.;Short, S. C.;Prise, K. M.
通讯作者：
Prise, K. M.
影响因子：
10.5
作者：
Kitagawa, R;Bakkenist, CJ;Kastan, MB
通讯作者：
Kastan, MB