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DOI | 10.1038/s41467-019-09723-8 |
Structural basis for recognition of 53BP1 tandem Tudor domain by TIRR | |
Dai, Yaxin1,2; Zhang, Aili3; Shan, Shan1; Gong, Zihua3; Zhou, Zheng1,2 | |
2019-04-15 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | Peoples R China; USA |
英文摘要 | P53-binding protein 1 (53BP1) regulates the double-strand break (DSB) repair pathway choice. A recently identified 53BP1-binding protein Tudor-interacting repair regulator (TIRR) modulates the access of 53BP1 to DSBs by masking the H4K20me2 binding surface on 53BP1, but the underlying mechanism remains unclear. Here we report the 1.76-A crystal structure of TIRR in complex with 53BP1 tandem Tudor domain. We demonstrate that the N-terminal region (residues 10-24) and the L8-loop of TIRR interact with 53BP1 Tudor through three loops (L1, L3, and L1'). TIRR recognition blocks H4K20me2 binding to 53BP1 Tudor and modulates 53BP1 functions in vivo. Structure comparisons identify a TIRR histidine (H106) that is absent from the TIRR homolog Nudt16, but essential for 53BP1 Tudor binding. Remarkably, mutations mimicking TIRR binding modules restore the disrupted binding of Nudt16-53BP1 Tudor. Our studies elucidate the mechanism by which TIRR recognizes 53BP1 Tudor and functions as a cellular inhibitor of the histone methyl-lysine readers. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000433299000006 |
WOS关键词 | DOUBLE-STRAND BREAKS ; DNA-DAMAGE SITES ; HOMOLOGOUS RECOMBINATION ; REPAIR ; RECRUITMENT ; SOFTWARE ; PATHWAY ; BINDING ; CHOICE ; BRCA1 |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204324 |
专题 | 资源环境科学 |
作者单位 | 1.Chinese Acad Sci, Inst Biophys, CAS Ctr Excellence Biomacromol, Natl Lab Biomacromol, Beijing 100101, Peoples R China; 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 3.Cleveland Clin, Lerner Res Inst, Dept Canc Biol, Cleveland, OH 44195 USA |
推荐引用方式 GB/T 7714 | Dai, Yaxin,Zhang, Aili,Shan, Shan,et al. Structural basis for recognition of 53BP1 tandem Tudor domain by TIRR[J]. NATURE COMMUNICATIONS,2019,9. |
APA | Dai, Yaxin,Zhang, Aili,Shan, Shan,Gong, Zihua,&Zhou, Zheng.(2019).Structural basis for recognition of 53BP1 tandem Tudor domain by TIRR.NATURE COMMUNICATIONS,9. |
MLA | Dai, Yaxin,et al."Structural basis for recognition of 53BP1 tandem Tudor domain by TIRR".NATURE COMMUNICATIONS 9(2019). |
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