Institut de Génétique Humaine, CNRS UMR9002, Université de Montpellier, Montpellier, France.
Doctoral School of Sciences and Technology-DSST, Rafic Hariri Campus, Lebanese University, Hadath, Lebanon.
Life Sci Alliance. 2023 Feb 6;6(4). doi: 10.26508/lsa.202101186. Print 2023 Apr.
Eukaryotic genomes are duplicated from thousands of replication origins that fire sequentially forming a defined spatiotemporal pattern of replication clusters. The temporal order of DNA replication is determined by chromatin architecture and, more specifically, by chromatin contacts that are stabilized by RIF1. Here, we show that RIF1 localizes near newly synthesized DNA. In cells exposed to the DNA replication inhibitor aphidicolin, suppression of RIF1 markedly decreased the efficacy of isolation of proteins on nascent DNA, suggesting that the isolation of proteins on nascent DNA procedure is biased by chromatin topology. RIF1 was required to limit the accumulation of DNA lesions induced by aphidicolin treatment and promoted the recruitment of cohesins in the vicinity of nascent DNA. Collectively, the data suggest that the stabilization of chromatin topology by RIF1 limits replication-associated genomic instability.
真核基因组由数千个复制起点复制而来，这些复制起点依次启动，形成一个有特定时空模式的复制簇。DNA 复制的时间顺序由染色质结构决定，更具体地说，由 RIF1 稳定的染色质接触决定。在这里，我们发现 RIF1 定位于新合成的 DNA 附近。在暴露于 DNA 复制抑制剂阿非迪霉素的细胞中，抑制 RIF1 显著降低了在新生 DNA 上分离蛋白质的效果，这表明在新生 DNA 上分离蛋白质的过程受到染色质拓扑结构的影响。RIF1 被需要限制阿非迪霉素处理引起的 DNA 损伤的积累，并促进黏合蛋白在新生 DNA 附近的募集。总的来说，这些数据表明 RIF1 通过稳定染色质拓扑结构来限制与复制相关的基因组不稳定性。
