Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy.
Department of Biology and Biotechnologies "C. Darwin", Sapienza University of Rome, 00185 Rome, Italy.
Int J Mol Sci. 2023 Feb 7;24(4):3248. doi: 10.3390/ijms24043248.
DNA double-strand breaks (DSBs) are harmful DNA lesions, which elicit catastrophic consequences for genome stability if not properly repaired. DSBs can be repaired by either non-homologous end joining (NHEJ) or homologous recombination (HR). The choice between these two pathways depends on which proteins bind to the DSB ends and how their action is regulated. NHEJ initiates with the binding of the Ku complex to the DNA ends, while HR is initiated by the nucleolytic degradation of the 5'-ended DNA strands, which requires several DNA nucleases/helicases and generates single-stranded DNA overhangs. DSB repair occurs within a precisely organized chromatin environment, where the DNA is wrapped around histone octamers to form the nucleosomes. Nucleosomes impose a barrier to the DNA end processing and repair machinery. Chromatin organization around a DSB is modified to allow proper DSB repair either by the removal of entire nucleosomes, thanks to the action of chromatin remodeling factors, or by post-translational modifications of histones, thus increasing chromatin flexibility and the accessibility of repair enzymes to the DNA. Here, we review histone post-translational modifications occurring around a DSB in the yeast and their role in DSB repair, with particular attention to DSB repair pathway choice.
DNA 双链断裂 (DSBs) 是有害的 DNA 损伤，如果不能正确修复，会对基因组稳定性造成灾难性的后果。DSBs 可以通过非同源末端连接 (NHEJ) 或同源重组 (HR) 来修复。这两种途径的选择取决于哪些蛋白质结合到 DSB 末端，以及它们的作用是如何被调节的。NHEJ 是由 Ku 复合物与 DNA 末端结合起始的，而 HR 则是由 5'-端 DNA 链的核酸酶/解旋酶的核切割起始的，这需要几种 DNA 核酸酶/解旋酶，并产生单链 DNA 突出端。DSB 修复发生在一个精确组织的染色质环境中，在这个环境中，DNA 缠绕在组蛋白八聚体周围形成核小体。核小体对 DNA 末端加工和修复机制构成了障碍。通过染色质重塑因子的作用，或者通过组蛋白的翻译后修饰，在 DSB 周围改变染色质的组织，以允许适当的 DSB 修复，从而增加染色质的灵活性和修复酶对 DNA 的可及性。在这里，我们综述了酵母中 DSB 周围发生的组蛋白翻译后修饰及其在 DSB 修复中的作用，特别关注 DSB 修复途径的选择。
