Phosphorylation of H2A.XTyr39 positively regulates DNA damage response and is linked to cancer progression

被引：25
作者：
Liu, Yan [1 ,2 ]
Long, Yue-Hong [1 ]
Wang, Shu-Qing [3 ]
Li, Yu-Feng [2 ]
Zhang, Jing-Hua [2 ]
机构：
[1] North China Univ Sci & Technol, Coll Life Sci, Tangshan, Peoples R China
[2] North China Univ Sci & Technol, Affiliated Tangshan Peoples Hosp, Inst Canc, Tangshan, Peoples R China
[3] Hosp North China Univ Sci & Technol, Tangshan 063000, Hebei, Peoples R China
来源：
FEBS Journal | 2016年 / 283卷 / 24期
基金：
中国国家自然科学基金;
关键词：
DSBs; EYA2; H2A.X; phosphorylation; DOUBLE-STRAND BREAKS; CELL SELF-RENEWAL; TARGETING EYA2; POOR-PROGNOSIS; HISTONE H2AX; GAMMA-H2AX; REPAIR; ATM; PROTEIN; MDC1;
D O I：
10.1111/febs.13951
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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.
引用
收藏
页码：4462 / 4473
页数：12
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