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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。
γH2AX, the 139th serine phosphorylated histone H2AX, has been generally recognized as a molecular marker of DNA double-strand breaks and is currently one of the focuses of research on DNA damage response mechanisms at home and abroad. γH2AX acts as a starting signal molecule for DNA double-strand break induction and recruits a series of DNA damaging reactive proteins to DNA damage sites to form DNA damage response functional complexes, which activate DNA repair reactions and cell cycle checkpoints . The timely dephosphorylation of γH2AX following the completion of DNA damage repair is crucial for the dissociation of the repair protein complex from the bound DNA and the release of cell cycle checkpoints. These findings led researchers to continually explore the mechanism of kinetic changes of γH2AX and its profound relationship with DNA damage repair. This review will discuss the molecular mechanisms by which the PI3K family catalyzes the phosphorylation of H2AX and the dephosphorylation of protein phosphatases such as PP2A, PP4, PP6 and Wip1 and their roles in DNA damage repair.