Kaya Veysel Oğulcan, Adebali Ogün
Molecular Biology, Genetics and Bioengineering Program, Sabanci University, Istanbul, Türkiye.
Nat Commun. 2025 Feb 5;16(1):1376. doi: 10.1038/s41467-024-55724-7.
While it is well-established that UV radiation threatens genomic integrity, the precise mechanisms by which cells orchestrate DNA damage response and repair within the context of 3D genome architecture remain unclear. Here, we address this gap by investigating the UV-induced reorganization of the 3D genome and its critical role in mediating damage response. Employing temporal maps of contact matrices and transcriptional profiles, we illustrate the immediate and holistic changes in genome architecture post-irradiation, emphasizing the significance of this reconfiguration for effective DNA repair processes. We demonstrate that UV radiation triggers a comprehensive restructuring of the 3D genome organization at all levels, including loops, topologically associating domains and compartments. Through the analysis of DNA damage and excision repair maps, we uncover a correlation between genome folding, gene regulation, damage formation probability, and repair efficacy. We show that adaptive reorganization of the 3D genome is a key mediator of the damage response, providing new insights into the complex interplay of genomic structure and cellular defense mechanisms against UV-induced damage, thereby advancing our understanding of cellular resilience.
虽然紫外线辐射会威胁基因组完整性这一点已得到充分证实，但在三维基因组结构背景下，细胞协调DNA损伤反应和修复的精确机制仍不清楚。在这里，我们通过研究紫外线诱导的三维基因组重组及其在介导损伤反应中的关键作用来填补这一空白。利用接触矩阵和转录谱的时间图谱，我们阐述了辐照后基因组结构的即时和整体变化，强调了这种重新配置对有效DNA修复过程的重要性。我们证明，紫外线辐射会在各个层面触发三维基因组组织的全面重组，包括环、拓扑相关结构域和区室。通过对DNA损伤和切除修复图谱的分析，我们发现了基因组折叠、基因调控、损伤形成概率和修复效率之间的相关性。我们表明，三维基因组的适应性重组是损伤反应的关键调节因子，为基因组结构与细胞抗紫外线损伤防御机制之间的复杂相互作用提供了新见解，从而加深了我们对细胞复原力的理解。
