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我们的前期研究在乳腺癌细胞SKBR3中首次检测到了组蛋白H2A.X第39位酪氨酸残基(Y39)可以发生磷酸化修饰(H2A.X~(Y39ph))。该位点的磷酸化修饰是γ-H2A.X正确形成的必要条件,并促进损伤修复因子募集到DNA损伤区域,有助于损伤修复反应。经过深入研究,我们又发现磷酸酶分子EYA2(eyes absent 2)能够去除乳腺癌细胞SKBR3中H2A.X~(Y39)位点的磷酸化修饰。在DNA损伤后,与H2A.X结合的EYA2蛋白减少,这可能是DNA损伤修复阶段H2A.X~(Y39ph)水平上调的原因。乳腺癌细胞中低水平的EYA2通过上调H2A.X~(Y39ph)水平及下游增殖相关基因转录促进细胞增殖。我们的报道为H2A.X~(Y39ph)功能的深入研究提供了数据基础。
Our previous study first detected the tyrosine residue (Y39) of histone H2A.X in breast cancer cell line SKBR3, which can undergo phosphorylation (H2A.X ~ (Y39ph)). Phosphorylation of this site is a necessary condition for the correct formation of γ-H2A.X, and promotes the recruitment of injury repair factors to the DNA damage area, helping to repair the repair reaction. After further study, we also found that the phosphatase molecule EYA2 (eyes absent 2) can remove phosphorylation of H2A.X ~ (Y39) in SKBR3 breast cancer cells. After DNA damage, the number of EYA2 protein binding to H2A.X decreased, which may be responsible for the up-regulation of H2A.X ~ (Y39ph) during DNA damage repair. Low levels of EYA2 in breast cancer cells promote cell proliferation by up-regulating the level of H2A.X ~ (Y39ph) and downstream proliferation-related gene transcription. Our report provides a data foundation for the in-depth study of H2A.X ~ (Y39ph) function.