53BP1：在 DNA 修复中选择。
53BP1: pro choice in DNA repair.
机构信息
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA; Central European Institute of Technology and Faculty of Science, Masaryk University, Brno, Czech Republic.
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
出版信息
Trends Cell Biol. 2014 Feb;24(2):108-17. doi: 10.1016/j.tcb.2013.09.003. Epub 2013 Oct 4.
Abstract
The DNA damage response factor 53BP1 functions at the intersection of two major double strand break (DSB) repair pathways--promoting nonhomologous end-joining (NHEJ) and inhibiting homology-directed repair (HDR)--and integrates cellular inputs to ensure their timely execution in the proper cellular contexts. Recent work has revealed that 53BP1 controls 5' end resection at DNA ends, mediates synapsis of DNA ends, promotes the mobility of damaged chromatin, improves DSB repair in heterochromatic regions, and contributes to lethal mis-repair of DSBs in BRCA1-deficient cells. Here we review these aspects of 53BP1 and discuss new data revealing how 53BP1 is loaded onto chromatin and uses its interacting factors Rif1 and PTIP to promote NHEJ and inhibit HDR.
摘要
DNA 损伤反应因子 53BP1 位于两条主要双链断裂 (DSB) 修复途径的交汇点——促进非同源末端连接 (NHEJ) 和抑制同源定向修复 (HDR)——并整合细胞输入，以确保在适当的细胞环境中及时执行它们。最近的研究表明，53BP1 控制 DNA 末端的 5'端切除，介导 DNA 末端的联会，促进受损染色质的迁移，提高异染色质区域的 DSB 修复，并有助于 BRCA1 缺陷细胞中 DSB 的致命错误修复。在这里，我们回顾了 53BP1 的这些方面，并讨论了新的数据，揭示了 53BP1 如何加载到染色质上，并利用其相互作用因子 Rif1 和 PTIP 来促进 NHEJ 和抑制 HDR。
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本文引用的文献
1
Replication timing regulation of eukaryotic replicons: Rif1 as a global regulator of replication timing.真核复制子复制定时的调控： Rif1 作为复制定时的全局调控因子。
Trends Genet. 2013 Aug;29(8):449-60. doi: 10.1016/j.tig.2013.05.001. Epub 2013 Jun 25.
2
53BP1 is a reader of the DNA-damage-induced H2A Lys 15 ubiquitin mark.53BP1 是 DNA 损伤诱导的 H2A 赖氨酸 15 泛素标记的读取器。
Nature. 2013 Jul 4;499(7456):50-4. doi: 10.1038/nature12318. Epub 2013 Jun 12.
3
53BP1 mediates productive and mutagenic DNA repair through distinct phosphoprotein interactions.53BP1 通过不同的磷酸化蛋白相互作用介导有性和诱变 DNA 修复。
Cell. 2013 Jun 6;153(6):1266-80. doi: 10.1016/j.cell.2013.05.023. Epub 2013 May 30.
4
The interaction between CtIP and BRCA1 is not essential for resection-mediated DNA repair or tumor suppression.CtIP 与 BRCA1 之间的相互作用对于切除介导的 DNA 修复或肿瘤抑制并非必需。
J Cell Biol. 2013 May 27;201(5):693-707. doi: 10.1083/jcb.201302145.
5
The deubiquitylating enzyme USP44 counteracts the DNA double-strand break response mediated by the RNF8 and RNF168 ubiquitin ligases.去泛素化酶 USP44 拮抗由 RNF8 和 RNF168 泛素连接酶介导的 DNA 双链断裂反应。
J Biol Chem. 2013 Jun 7;288(23):16579-16587. doi: 10.1074/jbc.M113.459917. Epub 2013 Apr 24.
6
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J Biol Chem. 2013 Apr 19;288(16):11135-43. doi: 10.1074/jbc.M113.457440. Epub 2013 Mar 13.
7
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8
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9
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10
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Mol Cell. 2013 Mar 7;49(5):858-71. doi: 10.1016/j.molcel.2013.01.002. Epub 2013 Jan 17.
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