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组蛋白H2A.X第139位丝氨酸磷酸化,形成γ-H2A.X。γ-H2A.X的正确形成对于DNA损伤修复、基因组稳定性和肿瘤发生至关重要,但其形成的机制仍不明确。我们在乳腺癌细胞SKBR3中检测到H2A.X的一种新的修饰方式——第39位酪氨酸残基(Y39)磷酸化,这是国内外首次报道这一修饰。经过一系列内源性和外源性实验证实,H2A.X Y39位点的磷酸化修饰(H2A.X~(Y39ph))是γ-H2A.X形成的必要前提条件。高水平的H2A.X~(Y39ph)能够促进乳腺癌细胞增殖,这一功能依赖于Nanog和Oct4及下游靶基因的转录水平上调。这一新修饰位点的阐明为肿瘤发生和DNA损伤反应中染色质重塑研究提供了新机制。
Histone H2A.X serine 139 phosphorylation, forming γ-H2A.X. The correct formation of γ-H2A.X is crucial for DNA damage repair, genomic stability and tumorigenesis, but the mechanism of its formation remains unclear. We detected a novel modification of H2A.X in breast cancer cell SKBR3 - tyrosine residue 39 (Y39) phosphorylation, which is the first report of this modification at home and abroad. After a series of endogenous and exogenous experiments confirmed that H2A.X Y39 phosphorylation site modification (H2A.X ~ (Y39ph)) is the necessary prerequisite for the formation of γ-H2A.X. High levels of H2A.X ~ (Y39ph) promote breast cancer cell proliferation, a function that is dependent on the upregulation of Nanog and Oct4 and downstream target genes. The elucidation of this new modification site provides a new mechanism for the study of chromatin remodeling in tumorigenesis and DNA damage response.