Department of Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, 421 Curie Blvd., Philadelphia, PA 19104-6160, USA.
FEBS Lett. 2011 Sep 16;585(18):2883-90. doi: 10.1016/j.febslet.2011.05.037. Epub 2011 May 27.
Considerable energetic investment is devoted to altering large stretches of chromatin adjacent to DNA double strand breaks (DSBs). Immediately ensuing DSB formation, a myriad of histone modifications are elicited to create a platform for inducible and modular assembly of DNA repair protein complexes in the vicinity of the DNA lesion. This complex signaling network is critical to repair DNA damage and communicate with cellular processes that occur in cis and in trans to the genomic lesion. Failure to properly execute DNA damage inducible chromatin changes is associated with developmental abnormalities, immunodeficiency, and malignancy in humans and in genetically engineered mouse models. This review will discuss current knowledge of DNA damage responsive histone changes that occur in mammalian cells, highlighting their involvement in the maintenance of genome integrity.
大量的能量投入被用于改变与 DNA 双链断裂(DSBs)相邻的大片染色质。在随后的 DSB 形成过程中,会引发大量组蛋白修饰,为诱导和模块化组装 DNA 修复蛋白复合物在 DNA 损伤部位提供一个平台。这个复杂的信号网络对于修复 DNA 损伤和与顺式和反式基因组损伤发生的细胞过程进行通讯至关重要。如果不能正确执行 DNA 损伤诱导的染色质变化,就会导致人类和基因工程小鼠模型中出现发育异常、免疫缺陷和恶性肿瘤。本文将讨论目前已知的哺乳动物细胞中对 DNA 损伤有反应的组蛋白变化,强调它们在维持基因组完整性方面的作用。