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A CDK-regulated chromatin segregase promoting chromosome replication
The replication of chromosomes during S phase is critical for cellular and organismal function. Replicative stress can result in genome instability, which is a major driver of cancer. Yet how chromatin is made accessible during eukaryotic DNA synthesis is poorly understood. Here, we report the chara...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410769/ https://www.ncbi.nlm.nih.gov/pubmed/34471130 http://dx.doi.org/10.1038/s41467-021-25424-7 |
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author | Chacin, Erika Bansal, Priyanka Reusswig, Karl-Uwe Diaz-Santin, Luis M. Ortega, Pedro Vizjak, Petra Gómez-González, Belen Müller-Planitz, Felix Aguilera, Andrés Pfander, Boris Cheung, Alan C. M. Kurat, Christoph F. |
author_facet | Chacin, Erika Bansal, Priyanka Reusswig, Karl-Uwe Diaz-Santin, Luis M. Ortega, Pedro Vizjak, Petra Gómez-González, Belen Müller-Planitz, Felix Aguilera, Andrés Pfander, Boris Cheung, Alan C. M. Kurat, Christoph F. |
author_sort | Chacin, Erika |
collection | PubMed |
description | The replication of chromosomes during S phase is critical for cellular and organismal function. Replicative stress can result in genome instability, which is a major driver of cancer. Yet how chromatin is made accessible during eukaryotic DNA synthesis is poorly understood. Here, we report the characterization of a chromatin remodeling enzyme—Yta7—entirely distinct from classical SNF2-ATPase family remodelers. Yta7 is a AAA(+) -ATPase that assembles into ~1 MDa hexameric complexes capable of segregating histones from DNA. The Yta7 chromatin segregase promotes chromosome replication both in vivo and in vitro. Biochemical reconstitution experiments using purified proteins revealed that the enzymatic activity of Yta7 is regulated by S phase-forms of Cyclin-Dependent Kinase (S-CDK). S-CDK phosphorylation stimulates ATP hydrolysis by Yta7, promoting nucleosome disassembly and chromatin replication. Our results present a mechanism for how cells orchestrate chromatin dynamics in co-ordination with the cell cycle machinery to promote genome duplication during S phase. |
format | Online Article Text |
id | pubmed-8410769 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-84107692021-09-22 A CDK-regulated chromatin segregase promoting chromosome replication Chacin, Erika Bansal, Priyanka Reusswig, Karl-Uwe Diaz-Santin, Luis M. Ortega, Pedro Vizjak, Petra Gómez-González, Belen Müller-Planitz, Felix Aguilera, Andrés Pfander, Boris Cheung, Alan C. M. Kurat, Christoph F. Nat Commun Article The replication of chromosomes during S phase is critical for cellular and organismal function. Replicative stress can result in genome instability, which is a major driver of cancer. Yet how chromatin is made accessible during eukaryotic DNA synthesis is poorly understood. Here, we report the characterization of a chromatin remodeling enzyme—Yta7—entirely distinct from classical SNF2-ATPase family remodelers. Yta7 is a AAA(+) -ATPase that assembles into ~1 MDa hexameric complexes capable of segregating histones from DNA. The Yta7 chromatin segregase promotes chromosome replication both in vivo and in vitro. Biochemical reconstitution experiments using purified proteins revealed that the enzymatic activity of Yta7 is regulated by S phase-forms of Cyclin-Dependent Kinase (S-CDK). S-CDK phosphorylation stimulates ATP hydrolysis by Yta7, promoting nucleosome disassembly and chromatin replication. Our results present a mechanism for how cells orchestrate chromatin dynamics in co-ordination with the cell cycle machinery to promote genome duplication during S phase. Nature Publishing Group UK 2021-09-01 /pmc/articles/PMC8410769/ /pubmed/34471130 http://dx.doi.org/10.1038/s41467-021-25424-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Chacin, Erika Bansal, Priyanka Reusswig, Karl-Uwe Diaz-Santin, Luis M. Ortega, Pedro Vizjak, Petra Gómez-González, Belen Müller-Planitz, Felix Aguilera, Andrés Pfander, Boris Cheung, Alan C. M. Kurat, Christoph F. A CDK-regulated chromatin segregase promoting chromosome replication |
title | A CDK-regulated chromatin segregase promoting chromosome replication |
title_full | A CDK-regulated chromatin segregase promoting chromosome replication |
title_fullStr | A CDK-regulated chromatin segregase promoting chromosome replication |
title_full_unstemmed | A CDK-regulated chromatin segregase promoting chromosome replication |
title_short | A CDK-regulated chromatin segregase promoting chromosome replication |
title_sort | cdk-regulated chromatin segregase promoting chromosome replication |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410769/ https://www.ncbi.nlm.nih.gov/pubmed/34471130 http://dx.doi.org/10.1038/s41467-021-25424-7 |
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