Ambrosio Susanna, Noviello Anna, Di Fusco Giovanni, Gorini Francesca, Piscone Anna, Amente Stefano, Majello Barbara
Department of Biology, University of Naples "Federico II", 80126 Naples, Italy.
Department of Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", 80131 Naples, Italy.
Cancers (Basel). 2025 Mar 11;17(6):949. doi: 10.3390/cancers17060949.
Genome stability is safeguarded by a finely orchestrated cascade of events that collectively represent the DNA damage response (DDR). In eukaryotes, the DDR operates within the dynamic chromatin landscape, where the interplay between DNA repair factors, chromatin remodeling, replication, transcription, spatial genome organization, and cytoskeletal forces is tightly coordinated. High-resolution studies have unveiled chromatin alterations spanning multiple scales, from localized kilobase-level changes to megabase-scale reorganization, which impact chromatin's physical properties and enhance the mobility of damaged regions. Leveraging this knowledge could pave the way for innovative therapeutic strategies, particularly in targeting chromatin dynamics to destabilize cancer cells selectively. This review, focusing on DNA double-strand breaks (DSBs), sheds light on how chromatin undergoes dynamic modifications in response to damage and how these changes influence the DDR at both local and global levels, offering a glimpse into how nuclear architecture contributes to the delicate balance between genome stability and adaptability and highlighting the importance of exploring these interactions in the context of cancer therapy.
基因组稳定性由一系列精心编排的事件来保障，这些事件共同构成了DNA损伤反应（DDR）。在真核生物中，DDR在动态染色质环境中发挥作用，其中DNA修复因子、染色质重塑、复制、转录、空间基因组组织和细胞骨架力之间的相互作用紧密协调。高分辨率研究揭示了跨越多个尺度的染色质改变，从局部千碱基水平的变化到兆碱基尺度的重组，这些改变影响染色质的物理性质并增强受损区域的流动性。利用这一知识可为创新治疗策略铺平道路，特别是在靶向染色质动力学以选择性地破坏癌细胞稳定性方面。本综述聚焦于DNA双链断裂（DSB），阐明了染色质如何响应损伤而进行动态修饰，以及这些变化如何在局部和全局水平影响DDR，让人得以一窥核结构如何促成基因组稳定性与适应性之间的微妙平衡，并强调了在癌症治疗背景下探索这些相互作用的重要性。
