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组蛋白2A变异体(histone family 2A variant,H2AX)在DNA双链断裂(double-strand break,DSB)损伤时可以发生不同的翻译后修饰,包括磷酸化、乙酰化、甲基化和泛素化。通过这些修饰,H2AX标记损伤的DNA双链,促进局部DNA修复因子和染色体重塑因子的募集,维持基因组的稳定性。这对于DSB的有效修复及细胞周期从周期检查点的恢复都是十分必要的。另外,H2AX在DSB信号通路必不可少的作用及其在肿瘤发生早期被激活事件,使它成为肿瘤生物学研究中的热点基因蛋白。本文中重点阐述近几年H2AX在DSB损伤修复中的研究进展,同时提出将它作为一个表观遗传标记,在人类肿瘤的早期诊断和治疗中的潜在应用价值。
Histone family 2A variant (H2AX) undergoes various post-translational modifications during DNA-double-strand break (DSB) injury including phosphorylation, acetylation, methylation and ubiquitination . Through these modifications, H2AX labeling of damaged DNA duplexes promotes recruitment of local DNA repair factors and chromosomal remodeling factors and maintains genomic stability. This is essential for effective repair of the DSB and recovery of the cell cycle from the periodic checkpoint. In addition, the essential role of H2AX in the DSB signaling pathway and its activation in the early stages of tumorigenesis make it a hot genetic protein in tumor biology research. This article focuses on the research progress of H2AX in DSB injury repair in recent years, and at the same time puts forward its potential application value as an epigenetic marker in the early diagnosis and treatment of human tumors.