CTCF prevents genomic instability by promoting homologous recombination-directed DNA double-strand break repair
文献类型：期刊论文
| 作者 | Li ZR2,3,6; Lang FC2,3,6; Li X2,3,6; Chen GJ2,3; zhoujm@mail.kiz.ac.cn; Lu DF2,3,6; Zheng WH2,3,6; Zhou JM*2,3; Shi P1,4,5; Fu JJ2,3,6 |
| 刊名 | Proc Natl Acad Sci U S A.
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| 出版日期 | 2017 |
| 卷号 | **期号:**页码:Epub ahead of print |
| 英文摘要 | 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. |
| 语种 | 英语 |
| 资助机构 | This work was supported by Strategic Priority Research Program of the Chinese Academy of Sciences Grants XDB13020400 and KSZD-EW-Z-009; Chinese Academy of Sciences Grant KSCXZ-EW-BR-6; Yunnan Provincial Government Grants 2011HA005, 2013FA051, and 2016FB039; and National Natural Science Foundation of China Grants 81471966, 81672040, U1602226, 2016YFC1200404 (to J.Z.), and 31601157 (to F.L.). ; This work was supported by Strategic Priority Research Program of the Chinese Academy of Sciences Grants XDB13020400 and KSZD-EW-Z-009; Chinese Academy of Sciences Grant KSCXZ-EW-BR-6; Yunnan Provincial Government Grants 2011HA005, 2013FA051, and 2016FB039; and National Natural Science Foundation of China Grants 81471966, 81672040, U1602226, 2016YFC1200404 (to J.Z.), and 31601157 (to F.L.). ; This work was supported by Strategic Priority Research Program of the Chinese Academy of Sciences Grants XDB13020400 and KSZD-EW-Z-009; Chinese Academy of Sciences Grant KSCXZ-EW-BR-6; Yunnan Provincial Government Grants 2011HA005, 2013FA051, and 2016FB039; and National Natural Science Foundation of China Grants 81471966, 81672040, U1602226, 2016YFC1200404 (to J.Z.), and 31601157 (to F.L.). ; This work was supported by Strategic Priority Research Program of the Chinese Academy of Sciences Grants XDB13020400 and KSZD-EW-Z-009; Chinese Academy of Sciences Grant KSCXZ-EW-BR-6; Yunnan Provincial Government Grants 2011HA005, 2013FA051, and 2016FB039; and National Natural Science Foundation of China Grants 81471966, 81672040, U1602226, 2016YFC1200404 (to J.Z.), and 31601157 (to F.L.). |
| 源URL | [http://159.226.149.26:8080/handle/152453/12045]  |
| 专题 | 昆明动物研究所_动物模型与人类重大疾病机理重点实验室 昆明动物研究所_遗传资源与进化国家重点实验室 昆明动物研究所_进化与功能基因组学 昆明动物研究所_基因调控与表达遗传 |
| 通讯作者 | zhoujm@mail.kiz.ac.cn |
| 作者单位 | 1.KIZ-SU Joint Laboratory of Animal Model and Drug Development, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China 2.Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China 3.Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China 4.State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China 5.Laboratory of Evolutionary and Functional Genomics, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China 6.Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650204, China 7.Institute of Health Sciences, Anhui University, Hefei 230601, China |
| 推荐引用方式 GB/T 7714 | Li ZR,Lang FC,Li X,et al. CTCF prevents genomic instability by promoting homologous recombination-directed DNA double-strand break repair[J]. Proc Natl Acad Sci U S A.,2017,**(**):Epub ahead of print. |
| APA | Li ZR.,Lang FC.,Li X.,Chen GJ.,zhoujm@mail.kiz.ac.cn.,...&Gong DH.(2017).CTCF prevents genomic instability by promoting homologous recombination-directed DNA double-strand break repair.Proc Natl Acad Sci U S A.,**(**),Epub ahead of print. |
| MLA | Li ZR,et al."CTCF prevents genomic instability by promoting homologous recombination-directed DNA double-strand break repair".Proc Natl Acad Sci U S A. **.**(2017):Epub ahead of print. |
入库方式： OAI收割
来源：昆明动物研究所
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