Fork coupling directs DNA replication elongation and termination

• 成果类型: Article
• 署名作者: Liu, Yang; Zhangding, Zhengrong; Liu, Xuhao; Gan, Tingting; Ai, Chen; Wu, Jinchun; Liang, Haoxin; Chen, Mohan; Guo, Yuefeng; Lu, Rusen; Jiang, Yongpeng; Ji, Xiong; Gao, Ning; Kong, Daochun; Li, Qing; Hu, Jiazhi
• 署名单位: Peking University; Peking University; Peking University; Peking University; Peking University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8777
• DOI: 10.1126/science.adj7606
• 发表日期: 2024-03-15
• 页码: 1215-1222
• 关键词: genome; DYNAMICS; origins; complex

摘要

DNA replication is initiated at multiple loci to ensure timely duplication of eukaryotic genomes. Sister replication forks progress bidirectionally, and replication terminates when two convergent forks encounter one another. To investigate the coordination of replication forks, we developed a replication-associated in situ HiC method to capture chromatin interactions involving nascent DNA. We identify more than 2000 fountain-like structures of chromatin contacts in human and mouse genomes, indicative of coupling of DNA replication forks. Replication fork interaction not only occurs between sister forks but also involves forks from two distinct origins to predetermine replication termination. Termination-associated chromatin fountains are sensitive to replication stress and lead to coupled forks-associated genomic deletions in cancers. These findings reveal the spatial organization of DNA replication forks within the chromatin context.