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Histone deposition promotes recombination-dependent replication at arrested forks

Replication stress poses a serious threat to genome stability. Recombination-Dependent-Replication (RDR) promotes DNA synthesis resumption from arrested forks. Despite the identification of chromatin restoration pathways after DNA repair, crosstalk coupling RDR and chromatin assembly is largely unex...

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Autores principales: Hardy, Julien, Dai, Dingli, Ait Saada, Anissia, Teixeira-Silva, Ana, Dupoiron, Louise, Mojallali, Fatemeh, Fréon, Karine, Ochsenbein, Francoise, Hartmann, Brigitte, Lambert, Sarah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6795475/
https://www.ncbi.nlm.nih.gov/pubmed/31584934
http://dx.doi.org/10.1371/journal.pgen.1008441
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author Hardy, Julien
Dai, Dingli
Ait Saada, Anissia
Teixeira-Silva, Ana
Dupoiron, Louise
Mojallali, Fatemeh
Fréon, Karine
Ochsenbein, Francoise
Hartmann, Brigitte
Lambert, Sarah
author_facet Hardy, Julien
Dai, Dingli
Ait Saada, Anissia
Teixeira-Silva, Ana
Dupoiron, Louise
Mojallali, Fatemeh
Fréon, Karine
Ochsenbein, Francoise
Hartmann, Brigitte
Lambert, Sarah
author_sort Hardy, Julien
collection PubMed
description Replication stress poses a serious threat to genome stability. Recombination-Dependent-Replication (RDR) promotes DNA synthesis resumption from arrested forks. Despite the identification of chromatin restoration pathways after DNA repair, crosstalk coupling RDR and chromatin assembly is largely unexplored. The fission yeast Chromatin Assembly Factor-1, CAF-1, is known to promote RDR. Here, we addressed the contribution of histone deposition to RDR. We expressed a mutated histone, H3-H113D, to genetically alter replication-dependent chromatin assembly by destabilizing (H3-H4)(2) tetramer. We established that DNA synthesis-dependent histone deposition, by CAF-1 and Asf1, promotes RDR by preventing Rqh1-mediated disassembly of joint-molecules. The recombination factor Rad52 promotes CAF-1 binding to sites of recombination-dependent DNA synthesis, indicating that histone deposition occurs downstream Rad52. Histone deposition and Rqh1 activity act synergistically to promote cell resistance to camptothecin, a topoisomerase I inhibitor that induces replication stress. Moreover, histone deposition favors non conservative recombination events occurring spontaneously in the absence of Rqh1, indicating that the stabilization of joint-molecules by histone deposition also occurs independently of Rqh1 activity. These results indicate that histone deposition plays an active role in promoting RDR, a benefit counterbalanced by stabilizing at-risk joint-molecules for genome stability.
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spelling pubmed-67954752019-10-19 Histone deposition promotes recombination-dependent replication at arrested forks Hardy, Julien Dai, Dingli Ait Saada, Anissia Teixeira-Silva, Ana Dupoiron, Louise Mojallali, Fatemeh Fréon, Karine Ochsenbein, Francoise Hartmann, Brigitte Lambert, Sarah PLoS Genet Research Article Replication stress poses a serious threat to genome stability. Recombination-Dependent-Replication (RDR) promotes DNA synthesis resumption from arrested forks. Despite the identification of chromatin restoration pathways after DNA repair, crosstalk coupling RDR and chromatin assembly is largely unexplored. The fission yeast Chromatin Assembly Factor-1, CAF-1, is known to promote RDR. Here, we addressed the contribution of histone deposition to RDR. We expressed a mutated histone, H3-H113D, to genetically alter replication-dependent chromatin assembly by destabilizing (H3-H4)(2) tetramer. We established that DNA synthesis-dependent histone deposition, by CAF-1 and Asf1, promotes RDR by preventing Rqh1-mediated disassembly of joint-molecules. The recombination factor Rad52 promotes CAF-1 binding to sites of recombination-dependent DNA synthesis, indicating that histone deposition occurs downstream Rad52. Histone deposition and Rqh1 activity act synergistically to promote cell resistance to camptothecin, a topoisomerase I inhibitor that induces replication stress. Moreover, histone deposition favors non conservative recombination events occurring spontaneously in the absence of Rqh1, indicating that the stabilization of joint-molecules by histone deposition also occurs independently of Rqh1 activity. These results indicate that histone deposition plays an active role in promoting RDR, a benefit counterbalanced by stabilizing at-risk joint-molecules for genome stability. Public Library of Science 2019-10-04 /pmc/articles/PMC6795475/ /pubmed/31584934 http://dx.doi.org/10.1371/journal.pgen.1008441 Text en © 2019 Hardy et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Hardy, Julien
Dai, Dingli
Ait Saada, Anissia
Teixeira-Silva, Ana
Dupoiron, Louise
Mojallali, Fatemeh
Fréon, Karine
Ochsenbein, Francoise
Hartmann, Brigitte
Lambert, Sarah
Histone deposition promotes recombination-dependent replication at arrested forks
title Histone deposition promotes recombination-dependent replication at arrested forks
title_full Histone deposition promotes recombination-dependent replication at arrested forks
title_fullStr Histone deposition promotes recombination-dependent replication at arrested forks
title_full_unstemmed Histone deposition promotes recombination-dependent replication at arrested forks
title_short Histone deposition promotes recombination-dependent replication at arrested forks
title_sort histone deposition promotes recombination-dependent replication at arrested forks
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6795475/
https://www.ncbi.nlm.nih.gov/pubmed/31584934
http://dx.doi.org/10.1371/journal.pgen.1008441
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