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...

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Autores principales: Bellelli, Roberto, Belan, Ondrej, Pye, Valerie E., Clement, Camille, Maslen, Sarah L., Skehel, J. Mark, Cherepanov, Peter, Almouzni, Genevieve, Boulton, Simon J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2018
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.
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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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