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Cohesin mediates DNA loop extrusion by a “swing and clamp” mechanism

Structural maintenance of chromosomes (SMC) complexes organize genome topology in all kingdoms of life and have been proposed to perform this function by DNA loop extrusion. How this process works is unknown. Here, we have analyzed how loop extrusion is mediated by human cohesin-NIPBL complexes, whi...

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Autores principales: Bauer, Benedikt W., Davidson, Iain F., Canena, Daniel, Wutz, Gordana, Tang, Wen, Litos, Gabriele, Horn, Sabrina, Hinterdorfer, Peter, Peters, Jan-Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8563363/
https://www.ncbi.nlm.nih.gov/pubmed/34624221
http://dx.doi.org/10.1016/j.cell.2021.09.016
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author Bauer, Benedikt W.
Davidson, Iain F.
Canena, Daniel
Wutz, Gordana
Tang, Wen
Litos, Gabriele
Horn, Sabrina
Hinterdorfer, Peter
Peters, Jan-Michael
author_facet Bauer, Benedikt W.
Davidson, Iain F.
Canena, Daniel
Wutz, Gordana
Tang, Wen
Litos, Gabriele
Horn, Sabrina
Hinterdorfer, Peter
Peters, Jan-Michael
author_sort Bauer, Benedikt W.
collection PubMed
description Structural maintenance of chromosomes (SMC) complexes organize genome topology in all kingdoms of life and have been proposed to perform this function by DNA loop extrusion. How this process works is unknown. Here, we have analyzed how loop extrusion is mediated by human cohesin-NIPBL complexes, which enable chromatin folding in interphase cells. We have identified DNA binding sites and large-scale conformational changes that are required for loop extrusion and have determined how these are coordinated. Our results suggest that DNA is translocated by a spontaneous 50 nm-swing of cohesin’s hinge, which hands DNA over to the ATPase head of SMC3, where upon binding of ATP, DNA is clamped by NIPBL. During this process, NIPBL “jumps ship” from the hinge toward the SMC3 head and might thereby couple the spontaneous hinge swing to ATP-dependent DNA clamping. These results reveal mechanistic principles of how cohesin-NIPBL and possibly other SMC complexes mediate loop extrusion.
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spelling pubmed-85633632021-11-09 Cohesin mediates DNA loop extrusion by a “swing and clamp” mechanism Bauer, Benedikt W. Davidson, Iain F. Canena, Daniel Wutz, Gordana Tang, Wen Litos, Gabriele Horn, Sabrina Hinterdorfer, Peter Peters, Jan-Michael Cell Article Structural maintenance of chromosomes (SMC) complexes organize genome topology in all kingdoms of life and have been proposed to perform this function by DNA loop extrusion. How this process works is unknown. Here, we have analyzed how loop extrusion is mediated by human cohesin-NIPBL complexes, which enable chromatin folding in interphase cells. We have identified DNA binding sites and large-scale conformational changes that are required for loop extrusion and have determined how these are coordinated. Our results suggest that DNA is translocated by a spontaneous 50 nm-swing of cohesin’s hinge, which hands DNA over to the ATPase head of SMC3, where upon binding of ATP, DNA is clamped by NIPBL. During this process, NIPBL “jumps ship” from the hinge toward the SMC3 head and might thereby couple the spontaneous hinge swing to ATP-dependent DNA clamping. These results reveal mechanistic principles of how cohesin-NIPBL and possibly other SMC complexes mediate loop extrusion. Cell Press 2021-10-14 /pmc/articles/PMC8563363/ /pubmed/34624221 http://dx.doi.org/10.1016/j.cell.2021.09.016 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Bauer, Benedikt W.
Davidson, Iain F.
Canena, Daniel
Wutz, Gordana
Tang, Wen
Litos, Gabriele
Horn, Sabrina
Hinterdorfer, Peter
Peters, Jan-Michael
Cohesin mediates DNA loop extrusion by a “swing and clamp” mechanism
title Cohesin mediates DNA loop extrusion by a “swing and clamp” mechanism
title_full Cohesin mediates DNA loop extrusion by a “swing and clamp” mechanism
title_fullStr Cohesin mediates DNA loop extrusion by a “swing and clamp” mechanism
title_full_unstemmed Cohesin mediates DNA loop extrusion by a “swing and clamp” mechanism
title_short Cohesin mediates DNA loop extrusion by a “swing and clamp” mechanism
title_sort cohesin mediates dna loop extrusion by a “swing and clamp” mechanism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8563363/
https://www.ncbi.nlm.nih.gov/pubmed/34624221
http://dx.doi.org/10.1016/j.cell.2021.09.016
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