| Title | The nucleoskeleton protein IFFO1 immobilizes broken DNA and suppresses chromosome translocation during tumorigenesis |
| Authors | Li, Wen Bai, Xiuzhen Li, Jun Zhao, Yichao Liu, Jingyan Zhao, Huayu Liu, Lan Ding, Miao Wang, Qingsong Shi, Fang-Yuan Hou, Mei Ji, Jianguo Gao, Ge Guo, Rong Sun, Yujie Liu, Yingfang Xu, Dongyi |
| Affiliation | Peking Univ, Sch Life Sci, State Key Lab Prot & Plant Gene Res, Beijing, Peoples R China Sun Yat Sen Univ, Sch Med, Guangzhou, Guangdong, Peoples R China Peking Univ, Sch Life Sci, Biodynam Opt Imaging Ctr, State Key Lab Membrane Biol, Beijing, Peoples R China Peking Univ, Beijing Adv Innovat Ctr Genom, Beijing, Peoples R China Sun Yat Sen Univ, Guangdong Prov Key Lab Colorectal & Pelv Floor Di, Affiliated Hosp 6, Sch Med, Guangzhou, Guangdong, Peoples R China |
| Issue Date | 2019 |
| Publisher | NATURE CELL BIOLOGY |
| Abstract | Chromosome translocation is a major cause of the onset and progression of diverse types of cancers. However, the mechanisms underlying this process remain poorly understood. Here, we identified a non-homologous end-joining protein, IFFO1, which structurally forms a heterotetramer with XRCC4. IFFO1 is recruited to the sites of DNA damage by XRCC4 and promotes the repair of DNA double-strand breaks in a parallel pathway with XLF. Interestingly, IFFO1 interacts with lamin A/C, forming an interior nucleoskeleton. Inactivating IFFO1 or its interaction with XRCC4 or lamin A/C leads to increases in both the mobility of broken ends and the frequency of chromosome translocation. Importantly, the destruction of this nucleoskeleton accounts for the elevated frequency of chromosome translocation in many types of cancer cells. Our results reveal that the lamin A/C-IFFO1-constituted nucleoskeleton prevents chromosome translocation by immobilizing broken DNA ends during tumorigenesis. |
| URI | http://hdl.handle.net/20.500.11897/544827 |
| ISSN | 1465-7392 |
| DOI | 10.1038/s41556-019-0388-0 |
| Indexed | SCI(E) EI |
| Appears in Collections: | 生命科学学院 膜生物学国家重点实验室 |
