DNA-PK：一种在多种 DSB 修复途径中发挥作用的动态酶。
DNA-PK: a dynamic enzyme in a versatile DSB repair pathway.
机构信息
Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, 2201 Inwood Road, Dallas, TX 75390, United States.
Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, 2201 Inwood Road, Dallas, TX 75390, United States.
出版信息
DNA Repair (Amst). 2014 May;17:21-9. doi: 10.1016/j.dnarep.2014.02.020. Epub 2014 Mar 27.
Abstract
DNA double stranded breaks (DSBs) are the most cytoxic DNA lesion as the inability to properly repair them can lead to genomic instability and tumorigenesis. The prominent DSB repair pathway in humans is non-homologous end-joining (NHEJ). In the simplest sense, NHEJ mediates the direct re-ligation of the broken DNA molecule. However, NHEJ is a complex and versatile process that can repair DSBs with a variety of damages and ends via the utilization of a significant number of proteins. In this review we will describe the important factors and mechanisms modulating NHEJ with emphasis given to the versatility of this repair process and the DNA-PK complex.
摘要
DNA 双链断裂（DSBs）是最具细胞毒性的 DNA 损伤，因为如果不能正确修复，可能会导致基因组不稳定和肿瘤发生。在人类中，突出的 DSB 修复途径是非同源末端连接（NHEJ）。从最简单的意义上说，NHEJ 介导断裂 DNA 分子的直接重新连接。然而，NHEJ 是一个复杂且多功能的过程，可以通过利用大量的蛋白质，用各种损伤和末端修复 DSB。在这篇综述中，我们将描述调节 NHEJ 的重要因素和机制，重点介绍该修复过程的多功能性和 DNA-PK 复合物。
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2
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Transl Cancer Res. 2013 Jun;2(3):130-143. doi: 10.3978/j.issn.2218-676X.2013.04.02.
3
A new method for high-resolution imaging of Ku foci to decipher mechanisms of DNA double-strand break repair.
J Cell Biol. 2013 Aug 5;202(3):579-95. doi: 10.1083/jcb.201303073. Epub 2013 Jul 29.
4
Functional intersection of ATM and DNA-dependent protein kinase catalytic subunit in coding end joining during V(D)J recombination.
Mol Cell Biol. 2013 Sep;33(18):3568-79. doi: 10.1128/MCB.00308-13. Epub 2013 Jul 8.
5
DNA double-strand-break complexity levels and their possible contributions to the probability for error-prone processing and repair pathway choice.
Nucleic Acids Res. 2013 Sep;41(16):7589-605. doi: 10.1093/nar/gkt556. Epub 2013 Jun 26.
6
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Adv Genet. 2013;82:1-45. doi: 10.1016/B978-0-12-407676-1.00001-9.
7
A method for systematic mapping of protein lysine methylation identifies functions for HP1β in DNA damage response.
Mol Cell. 2013 Jun 6;50(5):723-35. doi: 10.1016/j.molcel.2013.04.025. Epub 2013 May 23.
8
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10
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