DNA clamp function of the monoubiquitinated Fanconi anaemia ID complex

doi:10.1038/s41586-020-2110-6

GSTDTAP > 地球科学

DOI	10.1038/s41586-020-2110-6
	DNA clamp function of the monoubiquitinated Fanconi anaemia ID complex
	Wu, Thomas D.1; 39;Gorman, William E.2
	2020-02-26
发表期刊	NATURE
ISSN	0028-0836
EISSN	1476-4687
出版年	2020
卷号	580 期号:7802 页码:278-+
文章类型	Article
语种	英语
国家	USA
英文关键词	The ID complex, involving the proteins FANCI and FANCD2, is required for the repair of DNA interstrand crosslinks (ICL) and related lesions(1). These proteins are mutated in Fanconi anaemia, a disease in which patients are predisposed to cancer. The Fanconi anaemia pathway of ICL repair is activated when a replication fork stalls at an ICL2 this triggers monoubiquitination of the ID complex, in which one ubiquitin molecule is conjugated to each of FANCI and FANCD2. Monoubiquitination of ID is essential for ICL repair by excision, translesion synthesis and homologous recombination however, its function remains unknown(1,3). Here we report a cryo-electron microscopy structure of the monoubiquitinated human ID complex bound to DNA, and reveal that it forms a closed ring that encircles the DNA. By comparison with the structure of the non-ubiquitinated ID complex bound to ICL DNA-which we also report here-we show that monoubiquitination triggers a complete rearrangement of the open, trough-like ID structure through the ubiquitin of one protomer binding to the other protomer in a reciprocal fashion. These structures-together with biochemical data-indicate that the monoubiquitinated ID complex loses its preference for ICL and related branched DNA structures, and becomes a sliding DNA clamp that can coordinate the subsequent repair reactions. Our findings also reveal how monoubiquitination in general can induce an alternative protein structure with a new function. Cryo-EM structures of the FANCI-FANCD2 complex bound to DNA reveal that monoubiquitination triggers structural changes that enable the complex to function as a sliding DNA clamp and coordinate the repair of DNA interstrand crosslinks.
领域	地球科学 ; 气候变化 ; 资源环境
收录类别	SCI-E
WOS记录号	WOS:000519162500001
WOS关键词	CROSS-LINK REPAIR ; FANCD2 ; PROTEIN ; PATHWAY ; IDENTIFICATION ; MECHANISM ; BINDS ; SLX4
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
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/281104
专题	地球科学资源环境科学气候变化
作者单位	1.Genentech Inc, Dept Bioinformat & Computat Biol, San Francisco, CA 94080 USA; 2.Genentech Inc, Dept Canc Immunol, San Francisco, CA 94080 USA; 3.Genentech Inc, Dept Oncol Biomarker Dev, San Francisco, CA 94080 USA; 4.Genentech Inc, Dept Microchem Prote Lipid & Next Generat Sequenc, San Francisco, CA 94080 USA; 5.Genentech Inc, Dept OMNI Biomarker Dev, San Francisco, CA 94080 USA; 6.Genentech Inc, Dept Res Biol, San Francisco, CA 94080 USA; 7.Genentech Inc, Dept Dev Sci, San Francisco, CA 94080 USA; 8.Genentech Inc, Dept Pathol, San Francisco, CA 94080 USA; 9.ArsenalBio, San Francisco, CA 94080 USA
推荐引用方式 GB/T 7714	Wu, Thomas D.,39;Gorman, William E.. DNA clamp function of the monoubiquitinated Fanconi anaemia ID complex[J]. NATURE,2020,580(7802):278-+.
APA	Wu, Thomas D.,&39;Gorman, William E..(2020).DNA clamp function of the monoubiquitinated Fanconi anaemia ID complex.NATURE,580(7802),278-+.
MLA	Wu, Thomas D.,et al."DNA clamp function of the monoubiquitinated Fanconi anaemia ID complex".NATURE 580.7802(2020):278-+.