Dephosphorylation of the C-terminal Tyrosyl Residue of the DNA Damage-related Histone H2A.X Is Mediated by the Protein Phosphatase Eyes Absent
Dephosphorylation of the C-terminal Tyrosyl Residue of the DNA Damage-related Histone H2A.X Is Mediated by the Protein Phosphatase Eyes Absent
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DOI：
10.1074/jbc.c900032200
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发表时间：
2009-06-12
影响因子：
4.8
通讯作者：
Tonks, Nicholas K.
中科院分区：
文献类型：
--
作者：
Krishnan, Navasona;Jeong, Dae Gwin;Tonks, Nicholas K.
在哺乳动物细胞中，DNA损伤相关的组蛋白H2 A变体H2 A。X的特征在于C-末端酪氨酰残基Tyr-142，其被非典型激酶WSTF磷酸化。H2 A中Tyr-142的磷酸化状态。X已被证明是DNA损伤反应的重要调节剂，通过控制γ H2A.X焦点的形成，γ H2A.X焦点是招募参与DNA损伤修复和信号传导的分子的平台。在这项工作中，我们提出的证据来支持识别的眼睛缺席（EYA）磷酸酶，蛋白酪氨酸磷酸酶的卤酸脱卤酶超家族，负责去磷酸化的C-末端酪氨酰残基的组蛋白H2 A。X.我们证明EYA 2和EYA 3对H2 A的Tyr-142具有特异性。体外试验中的X。通过RNA干扰抑制eya 3导致基础磷酸化水平升高，并抑制DNA损伤诱导的H2 A的Tyr-142去磷酸化。体内X。这项研究提供了EYA磷酸酶的生理底物的第一个迹象，并建议这些酶在调节DNA损伤反应的新作用。
In mammalian cells, the DNA damage-related histone H2A variant H2A. X is characterized by a C-terminal tyrosyl residue, Tyr-142, which is phosphorylated by an atypical kinase, WSTF. The phosphorylation status of Tyr-142 in H2A. X has been shown to be an important regulator of the DNA damage response by controlling the formation of gamma H2A.X foci, which are platforms for recruiting molecules involved in DNA damage repair and signaling. In this work, we present evidence to support the identification of the Eyes Absent (EYA) phosphatases, protein-tyrosine phosphatases of the haloacid dehalogenase superfamily, as being responsible for dephosphorylating the C-terminal tyrosyl residue of histone H2A. X. We demonstrate that EYA2 and EYA3 displayed specificity for Tyr-142 of H2A. X in assays in vitro. Suppression of eya3 by RNA interference resulted in elevated basal phosphorylation and inhibited DNA damage-induced dephosphorylation of Tyr-142 of H2A. X in vivo. This study provides the first indication of a physiological substrate for the EYA phosphatases and suggests a novel role for these enzymes in regulation of the DNA damage response.