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Cryo-EM structure of 5-subunit Smc5/6 hinge region
Structural highlights
FunctionNSE2_YEAST Acts as an E3 ligase mediating SUMO/Smt3 attachment to SMC5 and YKU70. Acts in a DNA repair pathway for removal of UV-induced DNA damage that is distinct from classical nucleotide excision repair and in repair of ionizing radiation damage. Functions in homologous recombination repair of DNA double strand breaks and in recovery of stalled replication forks.[1] Publication Abstract from PubMedSmc5/6 is a member of the eukaryotic structural maintenance of chromosomes (SMC) family of complexes with important roles in genome maintenance and viral restriction. However, limited structural understanding of Smc5/6 hinders the elucidation of its diverse functions. Here, we report cryo-EM structures of the budding yeast Smc5/6 complex in eight-subunit, six-subunit and five-subunit states. Structural maps throughout the entire length of these complexes reveal modularity and key elements in complex assembly. We show that the non-SMC element (Nse)2 subunit supports the overall shape of the complex and uses a wedge motif to aid the stability and function of the complex. The Nse6 subunit features a flexible hook region for attachment to the Smc5 and Smc6 arm regions, contributing to the DNA repair roles of the complex. Our results also suggest a structural basis for the opposite effects of the Nse1-3-4 and Nse5-6 subcomplexes in regulating Smc5/6 ATPase activity. Collectively, our integrated structural and functional data provide a framework for understanding Smc5/6 assembly and function. Cryo-EM structures of Smc5/6 in multiple states reveal its assembly and functional mechanisms.,Li Q, Zhang J, Haluska C, Zhang X, Wang L, Liu G, Wang Z, Jin D, Cheng T, Wang H, Tian Y, Wang X, Sun L, Zhao X, Chen Z, Wang L Nat Struct Mol Biol. 2024 Jun 18. doi: 10.1038/s41594-024-01319-1. PMID:38890552[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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