H2AX磷酸化与去磷酸化的分子机制及其对DNA损伤修复反应的调节作用
发布时间：2018-12-16 12:09
【摘要】：γH2AX即第139位丝氨酸(ser)磷酸化的组蛋白H2AX已经被普遍认为是DNA双链断裂的分子标志,是目前国内外研究DNA损伤反应机制的焦点之一。γH2AX作为DNA双链断裂损伤感应的起始信号分子,将一系列DNA损伤反应蛋白募集到DNA损伤位点,形成DNA损伤反应功能复合物,启动激活DNA修复、细胞周期检查点等细胞DNA损伤反应。在DNA损伤修复结束后,γH2AX的及时去磷酸化,对于修复蛋白复合物从所结合的DNA上解离和细胞周期检查点的释放,都是至关重要的。这些发现促使研究人员不断地探索γH2AX的动力学变化机制及其与DNA损伤修复的深刻关系。本文将对PI3K家族催化H2AX的磷酸化及PP2A,PP4,PP6,Wip1等蛋白磷酸酶对其去磷酸化的分子机制,及其在DNA损伤修复中发挥作用的最新研究进展,作综述讨论。
[Abstract]:纬 H2AX, the histone H2AX phosphorylated at the 139th position serine (ser), has been widely regarded as a molecular marker of DNA double strand break. 纬 H2AX, as the initiation signal molecule of DNA double strand break damage induction, raises a series of DNA damage reaction proteins to DNA damage sites to form DNA damage response function complex. Activation of DNA repair, cell cycle checkpoint and other cell DNA damage response. After the repair of DNA damage, the timely dephosphorylation of 纬 H2AX is very important for the dissociation of the repair protein complex from the bound DNA and the release of the cell cycle checkpoint. These findings have prompted researchers to explore the mechanism of 纬 H2AX dynamics and its profound relationship with DNA damage repair. In this paper, the molecular mechanism of H2AX phosphorylation catalyzed by PI3K family and the dephosphorylation of H2AX by protein phosphatase such as PP2A,PP4,PP6,Wip1, as well as its recent progress in DNA damage repair, are reviewed and discussed.
【作者单位】： 安徽医科大学;军事医学科学院放射与辐射医学研究所;
【基金】：国家自然科学基金资助项目(81071361) 国家自然科学杰出青年基金资助项目(30825011)
【分类号】：R341
[Abstract]:纬 H2AX, the histone H2AX phosphorylated at the 139th position serine (ser), has been widely regarded as a molecular marker of DNA double strand break. 纬 H2AX, as the initiation signal molecule of DNA double strand break damage induction, raises a series of DNA damage reaction proteins to DNA damage sites to form DNA damage response function complex. Activation of DNA repair, cell cycle checkpoint and other cell DNA damage response. After the repair of DNA damage, the timely dephosphorylation of 纬 H2AX is very important for the dissociation of the repair protein complex from the bound DNA and the release of the cell cycle checkpoint. These findings have prompted researchers to explore the mechanism of 纬 H2AX dynamics and its profound relationship with DNA damage repair. In this paper, the molecular mechanism of H2AX phosphorylation catalyzed by PI3K family and the dephosphorylation of H2AX by protein phosphatase such as PP2A,PP4,PP6,Wip1, as well as its recent progress in DNA damage repair, are reviewed and discussed.
【作者单位】： 安徽医科大学;军事医学科学院放射与辐射医学研究所;
【基金】：国家自然科学基金资助项目(81071361) 国家自然科学杰出青年基金资助项目(30825011)
【分类号】：R341
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