Department of Medicine, University of Florida, Gainesville, Florida, USA.
Prog Mol Biol Transl Sci. 2012;110:207-27. doi: 10.1016/B978-0-12-387665-2.00008-0.
DNA damage occurs continuously as a result of various factors-intracellular metabolism, replication, and exposure to genotoxic agents, such as ionizing radiation and chemotherapy. If left unrepaired, this damage could result in changes or mutations within the cell genomic material. There are a number of different pathways that the cell can utilize to repair these DNA breaks. However, it is of utmost interest to know how the DNA damage is signaled to the various DNA pathways. As DNA damage occurs within the chromatin, we postulate that modifications of histones are important for signaling the position of DNA damage, recruiting the DNA repair proteins to the site of damage, and creating an open structure such that the repair proteins can access the site of damage. We discuss the modifications that occur on the histones and the manner in which they relate to the type of damage that has occurred as well as the DNA repair pathways that are activated.
DNA 损伤是由于各种因素不断产生的，包括细胞内代谢、复制以及暴露于致突变剂（如电离辐射和化疗药物）。如果不加以修复，这种损伤可能导致细胞基因组物质发生变化或突变。细胞可以利用多种不同的途径来修复这些 DNA 断裂。然而，了解 DNA 损伤如何向各种 DNA 途径发出信号是至关重要的。由于 DNA 损伤发生在染色质内，我们推测组蛋白的修饰对于信号传递 DNA 损伤的位置、将 DNA 修复蛋白招募到损伤部位以及形成开放结构以允许修复蛋白进入损伤部位非常重要。我们讨论了发生在组蛋白上的修饰以及它们与所发生的损伤类型以及激活的 DNA 修复途径的关系。
