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DNA 双链断裂修复后磷酸化组蛋白 H2AX 从染色质中消除的机制。

Mechanism of elimination of phosphorylated histone H2AX from chromatin after repair of DNA double-strand breaks.

机构信息

Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky ave., 194064 St. Petersburg, Russia.

出版信息

Mutat Res. 2010 Mar 1;685(1-2):54-60. doi: 10.1016/j.mrfmmm.2009.08.001. Epub 2009 Aug 12.

DOI:10.1016/j.mrfmmm.2009.08.001
PMID:19682466
Abstract

Covalent modifications of histones in chromatin play an important role in regulation of eukaryotic gene expression and DNA repair. Formation of double-strand breaks (DSBs) in DNA is followed by the rapid local phosphorylation of the C-terminal serine in the replacement histone H2AX in megabase chromatin domains around DSBs and formation of discrete nuclear foci called gammaH2AX foci. This epigenetic modification of chromatin represents the "histone code" for DNA damage signaling and repair and has been extensively studied during last decade. It is known that after DSB rejoining gammaH2AX foci are eliminated from the nucleus, but molecular mechanism of this elimination remains to be established. However, gammaH2AX elimination can serve as a useful marker of DSB repair in normal cells and tissues. In this paper the available data on kinetics and possible mechanisms of gammaH2AX elimination are reviewed.

摘要

染色质中组蛋白的共价修饰在真核基因表达和 DNA 修复的调控中起着重要作用。DNA 中双链断裂 (DSB) 的形成伴随着在 DSB 周围的兆碱基染色质域中替换组蛋白 H2AX 的 C 末端丝氨酸的快速局部磷酸化,以及形成离散的核焦点,称为 γH2AX 焦点。这种染色质的表观遗传修饰代表了 DNA 损伤信号转导和修复的“组蛋白密码”,在过去十年中得到了广泛研究。已知在 DSB 重连后,γH2AX 焦点从核内消除,但这种消除的分子机制尚待建立。然而,γH2AX 的消除可以作为正常细胞和组织中 DSB 修复的有用标记。本文综述了 γH2AX 消除的动力学和可能机制的现有数据。

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