Institut de Cancérologie de l'Ouest, Angers F-49055, France.
Department of Physics, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202.
Mol Biol Cell. 2024 Nov 1;35(11):ar136. doi: 10.1091/mbc.E24-04-0188. Epub 2024 Sep 18.
In yeasts and higher eukaryotes, chromatin motions may be tuned to genomic functions, with transcriptional activation and the DNA damage response both leading to profound changes in chromatin dynamics. The RAD51 recombinase is a key mediator of chromatin mobility following DNA damage. As functions of RAD51 beyond DNA repair are being discovered, we asked whether RAD51 modulates chromatin dynamics in the absence of DNA damage and found that inhibition or depletion of RAD51 alters chromatin motions in undamaged cells. Inhibition of RAD51 increased nucleosome clustering. Predictions from polymer models are that chromatin clusters reduce chain mobility and, indeed, we measured reduced motion of individual chromatin loci in cells treated with a RAD51 inhibitor. This effect was conserved in mammalian cells, yeasts, and plant cells. In contrast, RAD51 depletion or inhibition increased global chromatin motions at the microscale. The results uncover a role for RAD51 in regulating local and global chromatin dynamics independently from DNA damage and highlight the importance of considering different physical scales when studying chromatin dynamics.
在酵母和高等真核生物中,染色质运动可能与基因组功能相协调,转录激活和 DNA 损伤反应都会导致染色质动力学的深刻变化。RAD51 重组酶是 DNA 损伤后染色质流动性的关键介质。随着 RAD51 超越 DNA 修复功能的发现,我们想知道 RAD51 是否会在没有 DNA 损伤的情况下调节染色质动力学,并发现 RAD51 的抑制或耗竭会改变未受损细胞中的染色质运动。RAD51 的抑制会增加核小体聚集。聚合物模型的预测是,染色质簇会降低链的流动性,实际上,我们在用 RAD51 抑制剂处理的细胞中测量到单个染色质位点的运动减少。这种效应在哺乳动物细胞、酵母和植物细胞中都是保守的。相比之下,RAD51 的耗竭或抑制会增加微尺度上的整体染色质运动。研究结果揭示了 RAD51 在独立于 DNA 损伤调节局部和全局染色质动力学方面的作用,并强调了在研究染色质动力学时考虑不同物理尺度的重要性。