Shi Lei, Oberdoerffer Philipp
Mouse Cancer Genetics Program, NCI- Frederick, NIH, Frederick, MD 21702, USA.
Biochim Biophys Acta. 2012 Jul;1819(7):811-9. doi: 10.1016/j.bbagrm.2012.01.002. Epub 2012 Jan 17.
DNA double-strand breaks (DSBs) occur in the context of a highly organized chromatin environment and are, thus, a significant threat to the epigenomic integrity of eukaryotic cells. Changes in break-proximal chromatin structure are thought to be a prerequisite for efficient DNA repair and may help protect the structural integrity of the nucleus. Unlike most bona fide DNA repair factors, chromatin influences the repair process at several levels: the existing chromatin context at the site of damage directly affects the access and kinetics of the repair machinery; DSB induced chromatin modifications influence the choice of repair factors, thereby modulating repair outcome; lastly, DNA damage can have a significant impact on chromatin beyond the site of damage. We will discuss recent findings that highlight both the complexity and importance of dynamic and tightly orchestrated chromatin reorganization to ensure efficient DSB repair and nuclear integrity. This article is part of a Special Issue entitled: Chromatin in time and space.
DNA双链断裂(DSBs)发生在高度有序的染色质环境中,因此对真核细胞的表观基因组完整性构成重大威胁。断裂近端染色质结构的变化被认为是高效DNA修复的先决条件,可能有助于保护细胞核的结构完整性。与大多数真正的DNA修复因子不同,染色质在多个层面影响修复过程:损伤部位现有的染色质环境直接影响修复机制的进入和动力学;DSB诱导的染色质修饰影响修复因子的选择,从而调节修复结果;最后,DNA损伤对损伤部位以外的染色质也会产生重大影响。我们将讨论最近的研究发现,这些发现突出了动态且精心编排的染色质重组对于确保高效DSB修复和核完整性的复杂性和重要性。本文是名为“时空染色质”的特刊的一部分。