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高迁移率族蛋白B1:在碱基切除修复及相关功能中的作用

HMGB1: roles in base excision repair and related function.

作者信息

Liu Yuan, Prasad Rajendra, Wilson Samuel H

机构信息

Laboratory of Structural Biology, The National Institute of Environmental Health Sciences, National Institutes of Health, 111 T. W. Alexander Drive Research Triangle Park, NC 27709, USA.

出版信息

Biochim Biophys Acta. 2010 Jan-Feb;1799(1-2):119-30. doi: 10.1016/j.bbagrm.2009.11.008.

DOI:10.1016/j.bbagrm.2009.11.008
PMID:20123074
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2818529/
Abstract

High mobility group box 1 (HMGB1) is a nonhistone architectural protein that is involved in many biological processes including chromatin remodeling, transcription, cell signaling of inflammation, DNA damage repair and others. Recent studies have identified the cross-link of HMGB1 with a DNA base excision repair intermediate indicating that this protein is involved in base excision repair (BER) pathway. Further characterization of the roles of HMGB1 in BER demonstrates that the protein acts as a cofactor to regulate BER sub-pathways by inhibiting single-nucleotide BER and stimulating long-patch BER through modulating the activities of base excision repair enzymes. Directing of base lesion repair to the long-patch sub-pathway can result in trinucleotide repeat instability suggesting an important role of HMGB1 in modulating genome stability.

摘要

高迁移率族蛋白B1(HMGB1)是一种非组蛋白结构蛋白,参与许多生物学过程,包括染色质重塑、转录、炎症细胞信号传导、DNA损伤修复等。最近的研究发现HMGB1与DNA碱基切除修复中间体交联,表明该蛋白参与碱基切除修复(BER)途径。对HMGB1在BER中作用的进一步表征表明,该蛋白作为一种辅助因子,通过抑制单核苷酸BER并通过调节碱基切除修复酶的活性刺激长片段BER来调节BER子途径。将碱基损伤修复导向长片段子途径可导致三核苷酸重复不稳定,提示HMGB1在调节基因组稳定性中起重要作用。

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本文引用的文献

1
Coordination between polymerase beta and FEN1 can modulate CAG repeat expansion.聚合酶β与FEN1之间的协同作用可调节CAG重复序列的扩增。
J Biol Chem. 2009 Oct 9;284(41):28352-28366. doi: 10.1074/jbc.M109.050286. Epub 2009 Aug 11.
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Human HMGB1 directly facilitates interactions between nucleotide excision repair proteins on triplex-directed psoralen interstrand crosslinks.人高迁移率族蛋白B1直接促进三链定向补骨脂素链间交联上核苷酸切除修复蛋白之间的相互作用。
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Native HMGB1 protein inhibits repair of cisplatin-damaged nucleosomes in vitro.天然HMGB1蛋白在体外抑制顺铂损伤核小体的修复。
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Mol Carcinog. 2009 Jul;48(7):571-80. doi: 10.1002/mc.20544.
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Post-synthetic acetylation of HMGB1 protein modulates its interactions with supercoiled DNA.HMGB1蛋白的合成后乙酰化调节其与超螺旋DNA的相互作用。
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HMGB1 is a cofactor in mammalian base excision repair.高迁移率族蛋白B1是哺乳动物碱基切除修复中的一种辅助因子。
Mol Cell. 2007 Sep 7;27(5):829-41. doi: 10.1016/j.molcel.2007.06.029.
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