文章：

染色质结构与DNA损伤应答的相互作用与动态：综述

Interplay and Dynamics of Chromatin Architecture and DNA Damage Response: An Overview

原文发布日期：11 March 2025

DOI: 10.3390/cancers17060949

类型: Article

开放获取: 是

英文摘要：

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.

摘要翻译： 

基因组稳定性由一系列精密协调的事件所保障，这些事件共同构成了DNA损伤应答（DDR）。在真核生物中，DDR在动态的染色质环境中运行，其中DNA修复因子、染色质重塑、复制、转录、空间基因组组织以及细胞骨架力量之间的相互作用被紧密协调。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规模的重组——这些改变影响着染色质的物理特性并增强受损区域的流动性。利用这些知识可能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破坏癌细胞稳定性方面。本综述聚焦于DNA双链断裂（DSBs），阐明了染色质如何响应损伤而发生动态修饰，以及这些变化如何在局部和全局水平影响DDR，从而揭示核结构如何参与维持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。

原文链接：

Interplay and Dynamics of Chromatin Architecture and DNA Damage Response: An Overview