H2AX磷酸化與去磷酸化的分子機(jī)制及其對DNA損傷修復(fù)反應(yīng)的調(diào)節(jié)作用
發(fā)布時間：2018-12-16 12:09
【摘要】：γH2AX即第139位絲氨酸(ser)磷酸化的組蛋白H2AX已經(jīng)被普遍認(rèn)為是DNA雙鏈斷裂的分子標(biāo)志,是目前國內(nèi)外研究DNA損傷反應(yīng)機(jī)制的焦點(diǎn)之一。γH2AX作為DNA雙鏈斷裂損傷感應(yīng)的起始信號分子,將一系列DNA損傷反應(yīng)蛋白募集到DNA損傷位點(diǎn),形成DNA損傷反應(yīng)功能復(fù)合物,啟動激活DNA修復(fù)、細(xì)胞周期檢查點(diǎn)等細(xì)胞DNA損傷反應(yīng)。在DNA損傷修復(fù)結(jié)束后,γH2AX的及時去磷酸化,對于修復(fù)蛋白復(fù)合物從所結(jié)合的DNA上解離和細(xì)胞周期檢查點(diǎn)的釋放,都是至關(guān)重要的。這些發(fā)現(xiàn)促使研究人員不斷地探索γH2AX的動力學(xué)變化機(jī)制及其與DNA損傷修復(fù)的深刻關(guān)系。本文將對PI3K家族催化H2AX的磷酸化及PP2A,PP4,PP6,Wip1等蛋白磷酸酶對其去磷酸化的分子機(jī)制,及其在DNA損傷修復(fù)中發(fā)揮作用的最新研究進(jìn)展,作綜述討論。
[Abstract]:緯 H2AX, the histone H2AX phosphorylated at the 139th position serine (ser), has been widely regarded as a molecular marker of DNA double strand break. 緯 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 緯 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 緯 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.
【作者單位】： 安徽醫(yī)科大學(xué);軍事醫(yī)學(xué)科學(xué)院放射與輻射醫(yī)學(xué)研究所;
【基金】：國家自然科學(xué)基金資助項(xiàng)目(81071361) 國家自然科學(xué)杰出青年基金資助項(xiàng)目(30825011)
【分類號】：R341
[Abstract]:緯 H2AX, the histone H2AX phosphorylated at the 139th position serine (ser), has been widely regarded as a molecular marker of DNA double strand break. 緯 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 緯 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 緯 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.
【作者單位】： 安徽醫(yī)科大學(xué);軍事醫(yī)學(xué)科學(xué)院放射與輻射醫(yī)學(xué)研究所;
【基金】：國家自然科學(xué)基金資助項(xiàng)目(81071361) 國家自然科學(xué)杰出青年基金資助項(xiàng)目(30825011)
【分類號】：R341
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