Epigenetic modifications in double-strand break DNA damage signaling and repair.
Epigenetic modifications in double-strand break DNA damage signaling and repair.
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DOI：
10.1158/1078-0432.ccr-10-0513
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发表时间：
2010-09-15
期刊：
影响因子：
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通讯作者：
Côté J
中科院分区：
文献类型：
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作者：
Rossetto D;Truman AW;Kron SJ;Côté J
参与细胞对双链断裂（DSB）DNA损伤的反应的因子已被确定为潜在的治疗靶点，其将极大地使癌细胞对放射治疗和遗传毒性化学治疗敏感。它们可以使修复机制失效和/或恢复正常的细胞周期检查点，导致生长停滞、衰老和凋亡。现在很清楚，DNA损伤反应的一个主要方面是通过与染色质结构及其调节的特异性相互作用发生的。它涉及组蛋白的高度动态的翻译后修饰，这些修饰对于DNA损伤识别/信号传导、损伤修复和细胞周期停滞的释放至关重要。因此，靶向负责这些修饰的酶或阅读它们的蛋白质模块的药物具有非常高的治疗潜力。本文综述了真核生物DSB DNA损伤反应中染色质修饰及其作用的研究进展。
Factors involved in the cellular response to double strand break (DSB) DNA damage have been identified as potential therapeutic targets that would greatly sensitize cancer cells to radiotherapy and genotoxic chemotherapy. They could disable the repair machinery and/or reinstate normal cell cycle checkpoint leading to growth arrest, senescence and apoptosis. It is now clear that a major aspect of the DNA damage response occurs through specific interactions with chromatin structure and its modulation. It implicates highly dynamic post-translational modifications of histones that are critical for DNA damage recognition/signaling, repair of the lesion and release of cell cycle arrest. Therefore, drugs that target the enzymes responsible for these modifications or the protein modules reading them have very high therapeutic potential. This review presents the current state of knowledge on the different chromatin modifications and their roles in each step of eukaryotic DSB DNA damage response.