Department of Cancer Biology, Penn Center for Genome Integrity, Basser Center for BRCA, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Curr Opin Genet Dev. 2021 Dec;71:1-9. doi: 10.1016/j.gde.2021.05.006. Epub 2021 Jun 5.
Higher-order chromatin packing serves as a structural barrier to the recognition and repair of genomic lesions. The initiation and outcome of the repair response is dictated by a highly coordinated yet complex interplay between chromatin modifying enzymes and their cognate readers, damage induced chemical modifications, nucleosome density, transcriptional state, and cell cycle-dependent availability of DNA repair machinery. The physical and chemical properties of the DNA lesions themselves further regulate the nature of ensuing chromatin responses. Here we review recent discoveries across these various contexts, where chromatin regulates the homology-guided double-strand break repair mechanism, homologous recombination, and also highlight the key knowledge gaps vital to generate a holistic understanding of this process and its contributions to genome integrity.
高级染色质包装作为基因组损伤识别和修复的结构障碍。修复反应的启动和结果是由染色质修饰酶及其同源阅读器、损伤诱导的化学修饰、核小体密度、转录状态以及细胞周期中 DNA 修复机制的可用性之间高度协调但复杂的相互作用决定的。DNA 损伤本身的物理和化学性质进一步调节随后的染色质反应的性质。在这里,我们回顾了这些不同背景下的最新发现,其中染色质调节同源指导的双链断裂修复机制、同源重组,并且还强调了产生对该过程及其对基因组完整性的贡献的整体理解的关键知识空白的重要性。