Department of Radiation Oncology, University of Texas Southwestern Medical Center Dallas, TX, USA.
Front Oncol. 2013 Jan 22;2:214. doi: 10.3389/fonc.2012.00214. eCollection 2012.
In order to survive, cells have evolved highly effective repair mechanisms to deal with the potentially lethal DNA damage produced by exposure to endogenous as well as exogenous agents. Ionizing radiation exposure induces highly lethal DNA damage, especially DNA double-strand breaks (DSBs), that is sensed by the cellular machinery and then subsequently repaired by either of two different DSB repair mechanisms: (1) non-homologous end joining, which re-ligates the broken ends of the DNA and (2) homologous recombination, that employs an undamaged identical DNA sequence as a template, to maintain the fidelity of DNA repair. Repair of DSBs must occur within the natural context of the cellular DNA which, along with specific proteins, is organized to form chromatin, the overall structure of which can impede DNA damage site access by repair proteins. The chromatin complex is a dynamic structure and is known to change as required for ongoing cellular processes such as gene transcription or DNA replication. Similarly, during the process of DNA damage sensing and repair, chromatin needs to undergo several changes in order to facilitate accessibility of the repair machinery. Cells utilize several factors to modify the chromatin in order to locally open up the structure to reveal the underlying DNA sequence but post-translational modification of the histone components is one of the primary mechanisms. In this review, we will summarize chromatin modifications by the respective chromatin modifying factors that occur during the DNA damage response.
为了生存，细胞已经进化出了非常有效的修复机制来应对内源性和外源性物质暴露所产生的潜在致命 DNA 损伤。电离辐射暴露会诱导高度致命的 DNA 损伤，尤其是 DNA 双链断裂（DSB），这些损伤会被细胞机制感知，然后通过两种不同的 DSB 修复机制之一进行修复：（1）非同源末端连接，它重新连接 DNA 的断裂末端，（2）同源重组，它使用未受损的相同 DNA 序列作为模板，以保持 DNA 修复的保真度。DSB 的修复必须在细胞 DNA 的自然环境中进行，该 DNA 与特定蛋白质一起组织成染色质，其整体结构可能会阻碍修复蛋白对 DNA 损伤部位的接近。染色质复合物是一种动态结构，已知其会根据基因转录或 DNA 复制等持续的细胞过程进行所需的改变。同样，在 DNA 损伤感应和修复过程中，染色质需要发生几种变化，以便于修复机制的可及性。细胞利用几种因子来修饰染色质，以便局部打开结构以揭示潜在的 DNA 序列，但组蛋白成分的翻译后修饰是主要机制之一。在这篇综述中，我们将总结在 DNA 损伤反应过程中发生的由各自的染色质修饰因子引起的染色质修饰。
