科研成果
获奖成果
论文
专著
专利
现在位置:首页 > 科研成果 > 论文
论文
论文题目: CTCF Prevents Genomic Instability by Promoting Homologous Recombination-directed DNA Double-strand Break Repair
作者: Lang F, Li X, Zheng W, Li Z, Lu D, Chen G, Gong D, Yang L, Fu J, Shi P, Zhou J
联系作者: zhoujm@mail.kiz.ac.cn
发表年度: 2018
DOI: doi: 10.1073/pnas.1704076114
摘要:

CTCF is an essential epigenetic regulator mediating chromatin insulation, long-range regulatory interactions, and the organization of large topological domains in the nucleus. Phenotypes of CTCF haploinsufficient mutations in humans, knockout in mice, and depletion in cells are often consistent with impaired genome stability, but a role of CTCF in genome maintenance has not been fully investigated. Here, we report that CTCF maintains genome stability, is recruited to sites of DNA damage, and promotes homologous recombination repair of DNA double-strand breaks (DSBs). CTCF depletion increased chromosomal instability, marked by chromosome breakage and end fusions, elevated genotoxic stress-induced genomic DNA fragmentation, and activated the ataxia telangiectasia mutated (ATM) kinase. We show that CTCF could be recruited to drug-induced 53BP1 foci and known fragile sites, as well as to I-SceI endonuclease-induced DSBs. Laser irradiation analysis revealed that this recruitment depends on ATM, Nijmegen breakage syndrome (NBS), and the zinc finger DNA-binding domain of CTCF. We demonstrate that CTCF knockdown impaired homologous recombination (HR) repair of DSBs. Consistent with this, CTCF knockdown reduced the formation of γ-radiation-induced Rad51 foci, as well as the recruitment of Rad51 to laser-irradiated sites of DNA lesions and to I-SceI-induced DSBs. We further show that CTCF is associated with DNA HR repair factors MDC1 and AGO2, and directly interacts with Rad51 via its C terminus. These analyses establish a direct, functional role of CTCF in DNA repair and provide a potential link between genome organization and genome stability

刊物名称: Proceedings of the National Academy of Sciences of the United States of America
论文出处: http://www.pnas.org/content/114/41/10912.long
影响因子: 9.504(2017年 )