Conformational dynamics of cohesin/Scc2 loading complex are regulated by Smc3 acetylation and ATP binding

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Abstract

The ring-shaped cohesin complex is a key player in sister chromatid cohesion, DNA repair, and gene transcription. The loading of cohesin to chromosomes requires the loader Scc2 and is regulated by ATP. This process is hindered by Smc3 acetylation. However, the molecular mechanism underlying this inhibition remains mysterious. Here, using Saccharomyces cerevisiae as a model system, we identify a novel configuration of Scc2 with pre-engaged cohesin and reveal dynamic conformations of the cohesin/Scc2 complex in the loading reaction. We demonstrate that Smc3 acetylation blocks the association of Scc2 with pre-engaged cohesin by impairing the interaction of Scc2 with Smc3’s head. Lastly, we show that ATP binding induces the cohesin/Scc2 complex to clamp DNA by promoting the interaction between Scc2 and Smc3 coiled coil. Our results illuminate a dynamic reconfiguration of the cohesin/Scc2 complex during loading and indicate how Smc3 acetylation and ATP regulate this process.

Metadata

Authors/Creators:	Kaushik, A. https://orcid.org/0000-0003-0378-1378 Than, T. Petela, N.J. Voulgaris, M. Percival, C. https://orcid.org/0000-0001-7521-4132 Daniels, P. https://orcid.org/0000-0002-7216-8473 Rafferty, J.B. https://orcid.org/0000-0003-1183-7474 Nasmyth, K.A. Hu, B. https://orcid.org/0000-0001-6316-2830
Copyright, Publisher and Additional Information:	© The Author(s) 2023. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Dates:	Accepted: 11 September 2023 Published (online): 22 September 2023 Published: 22 September 2023
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Molecular Biology and Biotechnology (Sheffield) The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield)
Depositing User:	Symplectic Sheffield
Date Deposited:	27 Sep 2023 14:38
Last Modified:	27 Sep 2023 14:38
Status:	Published
Publisher:	Springer Science and Business Media LLC
Refereed:	Yes
Identification Number:	https://doi.org/10.1038/s41467-023-41596-w

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Conformational dynamics of cohesin/Scc2 loading complex are regulated by Smc3 acetylation and ATP binding. (deposited 11 Jan 2023 18:01)
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