A Structure-Based Mechanism for DNA Entry into the Cohesin Ring

Despite key roles in sister chromatid cohesion and chromosome organization, the mechanism by which cohesin rings are loaded onto DNA is still unknown. Here we combine biochemical approaches and cryoelectron microscopy (cryo-EM) to visualize a cohesin loading intermediate in which DNA is locked betwe...

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Published in:Molecular cell Vol. 79; no. 6; p. 917
Main Authors: Higashi, Torahiko L, Eickhoff, Patrik, Sousa, Joana S, Locke, Julia, Nans, Andrea, Flynn, Helen R, Snijders, Ambrosius P, Papageorgiou, George, O'Reilly, Nicola, Chen, Zhuo A, O'Reilly, Francis J, Rappsilber, Juri, Costa, Alessandro, Uhlmann, Frank
Format: Journal Article
Language:English
Published: United States 17.09.2020
Subjects:
Adenosine Triphosphatases - genetics
Cell Cycle Proteins - genetics
Cell Cycle Proteins - ultrastructure
Chromatids - genetics
Chromatids - ultrastructure
Chromosomal Proteins, Non-Histone - genetics
Chromosomal Proteins, Non-Histone - ultrastructure
Chromosome Segregation - genetics
Cohesins
Cryoelectron Microscopy
DNA - genetics
DNA - ultrastructure
Nucleic Acid Conformation
Protein Conformation
Saccharomyces cerevisiae - ultrastructure
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - ultrastructure
Sister Chromatid Exchange - genetics
ABC-ATPase
cohesin
SMC complexes
chromosome segregation
sister chromatid cohesion
S. pombe
DNA-protein crosslink mass spectrometry
Mis4/Scc2/NIPBL
DNA loop extrusion
cryo-electron microscopy
ISSN:1097-4164, 1097-4164
Online Access:Get more information
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Summary:Despite key roles in sister chromatid cohesion and chromosome organization, the mechanism by which cohesin rings are loaded onto DNA is still unknown. Here we combine biochemical approaches and cryoelectron microscopy (cryo-EM) to visualize a cohesin loading intermediate in which DNA is locked between two gates that lead into the cohesin ring. Building on this structural framework, we design experiments to establish the order of events during cohesin loading. In an initial step, DNA traverses an N-terminal kleisin gate that is first opened upon ATP binding and then closed as the cohesin loader locks the DNA against the ATPase gate. ATP hydrolysis will lead to ATPase gate opening to complete DNA entry. Whether DNA loading is successful or results in loop extrusion might be dictated by a conserved kleisin N-terminal tail that guides the DNA through the kleisin gate. Our results establish the molecular basis for cohesin loading onto DNA.
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ISSN:1097-4164
1097-4164
DOI:10.1016/j.molcel.2020.07.013