端粒蛋白 POT1、TRF1 和 TRF2 增强体外长补丁碱基切除修复。
Telomere proteins POT1, TRF1 and TRF2 augment long-patch base excision repair in vitro.
机构信息
Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
出版信息
Cell Cycle. 2012 Mar 1;11(5):998-1007. doi: 10.4161/cc.11.5.19483.
Abstract
Human telomeres consist of multiple tandem hexameric repeats, each containing a guanine triplet. Guanosine-rich clusters are highly susceptible to oxidative base damage, necessitating base excision repair (BER). Previous demonstration of enhanced strand displacement synthesis by the BER component DNA polymerase β in the presence of telomere protein TRF2 suggests that telomeres employ long-patch (LP) BER. Earlier analyses in vitro showed that efficiency of BER reactions is reduced in the DNA-histone environment of chromatin. Evidence presented here indicates that BER is promoted at telomeres. We found that the three proteins that contact telomere DNA, POT1, TRF1 and TRF2, enhance the rate of individual steps of LP-BER and stimulate the complete reconstituted LP-BER pathway. Thought to protect telomere DNA from degradation, these proteins still apparently evolved to allow selective access of repair proteins.
摘要
人类端粒由多个串联六聚体重复组成，每个重复包含一个鸟嘌呤三核苷酸。富含鸟嘌呤的簇极易受到氧化碱基损伤，需要碱基切除修复 (BER)。先前的研究表明，端粒蛋白 TRF2 存在时，BER 成分 DNA 聚合酶 β 增强链置换合成，表明端粒采用长补丁 (LP) BER。早期的体外分析表明，BER 反应的效率在染色质的 DNA-组蛋白环境中降低。本文提供的证据表明，BER 在端粒处得到促进。我们发现，与端粒 DNA 接触的三种蛋白质，POT1、TRF1 和 TRF2，可提高 LP-BER 各个步骤的速率，并刺激完整的 LP-BER 途径。这些蛋白质被认为可以保护端粒 DNA 免受降解，但它们显然仍在进化，以允许修复蛋白选择性进入。
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本文引用的文献
1
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DNA Repair (Amst). 2011 May 5;10(5):536-44. doi: 10.1016/j.dnarep.2011.03.001. Epub 2011 Apr 3.
2
Telomeric and extra-telomeric roles for telomerase and the telomere-binding proteins.端粒酶和端粒结合蛋白的端粒和端粒外作用。
Nat Rev Cancer. 2011 Mar;11(3):161-76. doi: 10.1038/nrc3025.
3
p53 governs telomere regulation feedback too, via TRF2.p53还通过TRF2调控端粒调节反馈。
Aging (Albany NY). 2011 Jan;3(1):26-32. doi: 10.18632/aging.100271.
4
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Biochemistry. 2011 Jan 11;50(1):136-43. doi: 10.1021/bi1017667. Epub 2010 Dec 14.
5
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Aging (Albany NY). 2010 Oct;2(10):691-708. doi: 10.18632/aging.100210.
6
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7
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DNA Repair (Amst). 2011 Jan 2;10(1):34-44. doi: 10.1016/j.dnarep.2010.09.008. Epub 2010 Oct 16.
9
WITHDRAWN: Oxidative stress in aging: Theoretical outcomes and clinical evidences in humans.撤回：衰老中的氧化应激：人类的理论结果与临床证据
Biomed Pharmacother. 2010 Sep 25. doi: 10.1016/j.biopha.2010.09.010.
10
Taking apart Rap1: an adaptor protein with telomeric and non-telomeric functions.剖析 Rap1：一种具有端粒和非端粒功能的衔接蛋白。
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