POLE3-POLE4 Is a Histone H3-H4 Chaperone that Maintains Chromatin Integrity during DNA Replication
Maintenance of epigenetic integrity relies on coordinated recycling and partitioning of parental histones and deposition of newly synthesized histones during DNA replication. This process depends upon a poorly characterized network of histone chaperones, remodelers, and binding proteins. Here we imp...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6179962/ https://www.ncbi.nlm.nih.gov/pubmed/30217558 http://dx.doi.org/10.1016/j.molcel.2018.08.043 |
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author | Bellelli, Roberto Belan, Ondrej Pye, Valerie E. Clement, Camille Maslen, Sarah L. Skehel, J. Mark Cherepanov, Peter Almouzni, Genevieve Boulton, Simon J. |
author_facet | Bellelli, Roberto Belan, Ondrej Pye, Valerie E. Clement, Camille Maslen, Sarah L. Skehel, J. Mark Cherepanov, Peter Almouzni, Genevieve Boulton, Simon J. |
author_sort | Bellelli, Roberto |
collection | PubMed |
description | Maintenance of epigenetic integrity relies on coordinated recycling and partitioning of parental histones and deposition of newly synthesized histones during DNA replication. This process depends upon a poorly characterized network of histone chaperones, remodelers, and binding proteins. Here we implicate the POLE3-POLE4 subcomplex of the leading-strand polymerase, Polε, in replication-coupled nucleosome assembly through its ability to selectively bind to histones H3-H4. Using hydrogen/deuterium exchange mass spectrometry and physical mapping, we define minimal domains necessary for interaction between POLE3-POLE4 and histones H3-H4. Biochemical analyses establish that POLE3-POLE4 is a histone chaperone that promotes tetrasome formation and DNA supercoiling in vitro. In cells, POLE3-POLE4 binds both newly synthesized and parental histones, and its depletion hinders helicase unwinding and chromatin PCNA unloading and compromises coordinated parental histone retention and new histone deposition. Collectively, our study reveals that POLE3-POLE4 possesses intrinsic H3-H4 chaperone activity, which facilitates faithful nucleosome dynamics at the replication fork. |
format | Online Article Text |
id | pubmed-6179962 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-61799622018-10-12 POLE3-POLE4 Is a Histone H3-H4 Chaperone that Maintains Chromatin Integrity during DNA Replication Bellelli, Roberto Belan, Ondrej Pye, Valerie E. Clement, Camille Maslen, Sarah L. Skehel, J. Mark Cherepanov, Peter Almouzni, Genevieve Boulton, Simon J. Mol Cell Article Maintenance of epigenetic integrity relies on coordinated recycling and partitioning of parental histones and deposition of newly synthesized histones during DNA replication. This process depends upon a poorly characterized network of histone chaperones, remodelers, and binding proteins. Here we implicate the POLE3-POLE4 subcomplex of the leading-strand polymerase, Polε, in replication-coupled nucleosome assembly through its ability to selectively bind to histones H3-H4. Using hydrogen/deuterium exchange mass spectrometry and physical mapping, we define minimal domains necessary for interaction between POLE3-POLE4 and histones H3-H4. Biochemical analyses establish that POLE3-POLE4 is a histone chaperone that promotes tetrasome formation and DNA supercoiling in vitro. In cells, POLE3-POLE4 binds both newly synthesized and parental histones, and its depletion hinders helicase unwinding and chromatin PCNA unloading and compromises coordinated parental histone retention and new histone deposition. Collectively, our study reveals that POLE3-POLE4 possesses intrinsic H3-H4 chaperone activity, which facilitates faithful nucleosome dynamics at the replication fork. Cell Press 2018-10-04 /pmc/articles/PMC6179962/ /pubmed/30217558 http://dx.doi.org/10.1016/j.molcel.2018.08.043 Text en Crown Copyright © 2018 Published by Elsevier Inc. All rights reserved. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Bellelli, Roberto Belan, Ondrej Pye, Valerie E. Clement, Camille Maslen, Sarah L. Skehel, J. Mark Cherepanov, Peter Almouzni, Genevieve Boulton, Simon J. POLE3-POLE4 Is a Histone H3-H4 Chaperone that Maintains Chromatin Integrity during DNA Replication |
title | POLE3-POLE4 Is a Histone H3-H4 Chaperone that Maintains Chromatin Integrity during DNA Replication |
title_full | POLE3-POLE4 Is a Histone H3-H4 Chaperone that Maintains Chromatin Integrity during DNA Replication |
title_fullStr | POLE3-POLE4 Is a Histone H3-H4 Chaperone that Maintains Chromatin Integrity during DNA Replication |
title_full_unstemmed | POLE3-POLE4 Is a Histone H3-H4 Chaperone that Maintains Chromatin Integrity during DNA Replication |
title_short | POLE3-POLE4 Is a Histone H3-H4 Chaperone that Maintains Chromatin Integrity during DNA Replication |
title_sort | pole3-pole4 is a histone h3-h4 chaperone that maintains chromatin integrity during dna replication |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6179962/ https://www.ncbi.nlm.nih.gov/pubmed/30217558 http://dx.doi.org/10.1016/j.molcel.2018.08.043 |
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