Center for Molecular Medicine, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands.
Center for Molecular Medicine, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands.
DNA Repair (Amst). 2024 Jan;133:103592. doi: 10.1016/j.dnarep.2023.103592. Epub 2023 Nov 16.
Eukaryotic nuclei are constantly being exposed to factors that break or chemically modify the DNA. Accurate repair of this DNA damage is crucial to prevent DNA mutations and maintain optimal cell function. To overcome the detrimental effects of DNA damage, a multitude of repair pathways has evolved. These pathways need to function properly within the different chromatin domains present in the nucleus. Each of these domains exhibit distinct molecular- and bio-physical characteristics that can influence the response to DNA damage. In particular, chromatin domains highly enriched for repetitive DNA sequences, such as nucleoli, centromeres and pericentromeric heterochromatin require tailored repair mechanisms to safeguard genome stability. Work from the past decades has led to the development of innovative imaging tools as well as inducible DNA damage techniques to gain new insights into the impact of these repetitive chromatin domains on the DNA repair process. Here we summarize these tools with a particular focus on Double-Strand Break (DSB) repair, and discuss the insights gained into our understanding of the influence of chromatin domains on DSB -dynamics and -repair pathway choice.
真核细胞核不断受到破坏或化学修饰 DNA 的因素的影响。准确修复这种 DNA 损伤对于防止 DNA 突变和维持最佳细胞功能至关重要。为了克服 DNA 损伤的有害影响，已经进化出多种修复途径。这些途径需要在核内存在的不同染色质域内正常发挥作用。这些域中的每一个都表现出独特的分子和生物物理特性，这可能会影响对 DNA 损伤的反应。特别是富含重复 DNA 序列的染色质域，如核仁、着丝粒和着丝粒周围异染色质，需要定制的修复机制来保护基因组稳定性。过去几十年的工作导致了创新成像工具和诱导性 DNA 损伤技术的发展，以深入了解这些重复染色质域对 DNA 修复过程的影响。在这里，我们总结了这些工具，特别关注双链断裂 (DSB) 修复，并讨论了对染色质域对 DSB 动力学和修复途径选择影响的理解的深入认识。
