Cryo-EM Structures of Smc5/6 in Multiple States Reveal Its Assembly and Functional Mechanisms
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Molecular Biology
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Smc5/6 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.
All eukaryotic SMC proteins induce a twist of -0.6 at each DNA loop extrusion step.
Janissen R, Barth R, Davidson I, Peters J, Dekker C Sci Adv. 2024; 10(50):eadt1832.
PMID: 39671477 PMC: 11641105. DOI: 10.1126/sciadv.adt1832.