Phosphorylation of H2A.XTyr39 positively regulates DNA damage response and is linked to cancer progression
Phosphorylation of H2A.XTyr39 positively regulates DNA damage response and is linked to cancer progression
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DOI：
10.1111/febs.13951
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发表时间：
2016-12-01
期刊：
影响因子：
5.4
通讯作者：
Zhang, Jing-Hua
中科院分区：
文献类型：
--
作者：
Liu, Yan;Long, Yue-Hong;Zhang, Jing-Hua
双链DNA断裂诱导组蛋白H2A丝氨酸磷酸化。X产生- h2a。X病灶然后被DNA损伤反应途径蛋白识别。h2a的形成。因此，X对于DNA双链断裂的修复和基因组稳定性的维持至关重要，双链断裂的识别或修复缺陷可导致肿瘤发生。然而，关于伽马- h2a形成的关键细节。X及其在肿瘤发生中的可能作用仍不清楚。在这里，我们报道了H2A上一个以前未知的磷酸化位点。X, Tyr39。这个位点的磷酸化是由电离辐射诱导的，是γ - h2a的先决条件。X的形成。H2A磷酸化增加。在多种肿瘤细胞系中观察到Tyr39位点的X，我们发现H2AX Tyr39磷酸化与组织学分级、肿瘤大小、肿瘤淋巴结转移分期呈正相关，与生存负相关。我们还发现了眼缺失2 （EYA2）在调节H2A中的潜在作用。X Tyr39磷酸化。我们的研究支持H2AX Tyr39磷酸化在γ - h2a中的重要作用。X形成和癌症进展。
Double-stranded DNA breaks induce serine phosphorylation of histone H2A.X, producing gamma-H2A. X foci that are then recognized by DNA damage response pathway proteins. Formation of gamma-H2A. X is therefore critical for the repair of DNA double-stranded breaks and maintenance of genomic stability, and defects in the recognition or repair of double-stranded breaks can result in tumorigenesis. However, key details regarding the formation of gamma-H2A.X and its possible role in tumorigenesis remain elusive. Here, we report a previously unknown phosphorylation site on H2A.X, Tyr39. Phosphorylation at this site is induced by ionizing radiation and is a prerequisite for gamma-H2A. X formation. Increased phosphorylation of H2A.X at Tyr39 was observed in multiple cancer cell lines, and we found that H2AX Tyr39 phosphorylation positively correlated with histological grade, tumor size and tumor node metastasis stage, and negatively correlated with survival. We also identified a potential role for eyes absent 2 (EYA2) in regulating H2A. X Tyr39 phosphorylation. Our study supports an important role for H2AX Tyr39 phosphorylation in gamma-H2A.X formation and cancer progression.