Chromosome Stability and Dynamics Unit, Department of Disease Biology, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark.
Curr Opin Genet Dev. 2013 Apr;23(2):156-65. doi: 10.1016/j.gde.2012.11.001. Epub 2013 Jan 9.
Chromatin modifications in response to DNA damage are vital for genome integrity. Multiple proteins and pathways required to generate specialized chromatin domains around DNA lesions have been identified and the increasing amount of information calls for unifying concepts that would allow us to grasp the ever-increasing complexity. This review aims at contributing to this trend by focusing on feed-forward and feedback mechanisms, which in mammalian cells determine the extent of chromatin modifications after DNA damage. We highlight the emerging notion that the nodal points of these highly dynamic pathways operate in a rate-limiting mode, whose deregulation can disrupt physiological boundaries between damaged and undamaged chromatin, dictate repair pathway choice, and determine the fate of cells exposed to genotoxic stress.
染色质修饰对于应对 DNA 损伤至关重要，它是基因组完整性的基础。为了在 DNA 损伤周围产生特定的染色质区域，已经鉴定出了多种蛋白质和途径，并且随着信息量的不断增加，我们需要将这些信息整合到统一的概念中，以帮助我们理解日益复杂的情况。本综述旨在通过关注正反馈和负反馈机制，为这一趋势做出贡献，这些机制决定了哺乳动物细胞在 DNA 损伤后染色质修饰的程度。我们强调了一个新的观点，即这些高度动态途径的节点以限速模式运作，其失调可能会破坏受损和未受损染色质之间的生理边界，决定修复途径的选择，并决定暴露于遗传毒性应激下的细胞的命运。
