The nuclear pore primes recombination-dependent DNA synthesis at arrested forks by promoting SUMO removal

Nuclear Pore complexes (NPCs) act as docking sites to anchor particular DNA lesions facilitating DNA repair by elusive mechanisms. Using replication fork barriers in fission yeast, we report that relocation of arrested forks to NPCs occurred after Rad51 loading and its enzymatic activity. The E3 SUM...

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Autores principales: Kramarz, Karol, Schirmeisen, Kamila, Boucherit, Virginie, Ait Saada, Anissia, Lovo, Claire, Palancade, Benoit, Freudenreich, Catherine, Lambert, Sarah A. E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648084/
https://www.ncbi.nlm.nih.gov/pubmed/33159083
http://dx.doi.org/10.1038/s41467-020-19516-z
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author Kramarz, Karol
Schirmeisen, Kamila
Boucherit, Virginie
Ait Saada, Anissia
Lovo, Claire
Palancade, Benoit
Freudenreich, Catherine
Lambert, Sarah A. E.
author_facet Kramarz, Karol
Schirmeisen, Kamila
Boucherit, Virginie
Ait Saada, Anissia
Lovo, Claire
Palancade, Benoit
Freudenreich, Catherine
Lambert, Sarah A. E.
author_sort Kramarz, Karol
collection PubMed
description Nuclear Pore complexes (NPCs) act as docking sites to anchor particular DNA lesions facilitating DNA repair by elusive mechanisms. Using replication fork barriers in fission yeast, we report that relocation of arrested forks to NPCs occurred after Rad51 loading and its enzymatic activity. The E3 SUMO ligase Pli1 acts at arrested forks to safeguard integrity of nascent strands and generates poly-SUMOylation which promote relocation to NPCs but impede the resumption of DNA synthesis by homologous recombination (HR). Anchorage to NPCs allows SUMO removal by the SENP SUMO protease Ulp1 and the proteasome, promoting timely resumption of DNA synthesis. Preventing Pli1-mediated SUMO chains was sufficient to bypass the need for anchorage to NPCs and the inhibitory effect of poly-SUMOylation on HR-mediated DNA synthesis. Our work establishes a novel spatial control of Recombination-Dependent Replication (RDR) at a unique sequence that is distinct from mechanisms engaged at collapsed-forks and breaks within repeated sequences.
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spelling pubmed-76480842020-11-10 The nuclear pore primes recombination-dependent DNA synthesis at arrested forks by promoting SUMO removal Kramarz, Karol Schirmeisen, Kamila Boucherit, Virginie Ait Saada, Anissia Lovo, Claire Palancade, Benoit Freudenreich, Catherine Lambert, Sarah A. E. Nat Commun Article Nuclear Pore complexes (NPCs) act as docking sites to anchor particular DNA lesions facilitating DNA repair by elusive mechanisms. Using replication fork barriers in fission yeast, we report that relocation of arrested forks to NPCs occurred after Rad51 loading and its enzymatic activity. The E3 SUMO ligase Pli1 acts at arrested forks to safeguard integrity of nascent strands and generates poly-SUMOylation which promote relocation to NPCs but impede the resumption of DNA synthesis by homologous recombination (HR). Anchorage to NPCs allows SUMO removal by the SENP SUMO protease Ulp1 and the proteasome, promoting timely resumption of DNA synthesis. Preventing Pli1-mediated SUMO chains was sufficient to bypass the need for anchorage to NPCs and the inhibitory effect of poly-SUMOylation on HR-mediated DNA synthesis. Our work establishes a novel spatial control of Recombination-Dependent Replication (RDR) at a unique sequence that is distinct from mechanisms engaged at collapsed-forks and breaks within repeated sequences. Nature Publishing Group UK 2020-11-06 /pmc/articles/PMC7648084/ /pubmed/33159083 http://dx.doi.org/10.1038/s41467-020-19516-z Text en © The Author(s) 2020 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/.
spellingShingle Article
Kramarz, Karol
Schirmeisen, Kamila
Boucherit, Virginie
Ait Saada, Anissia
Lovo, Claire
Palancade, Benoit
Freudenreich, Catherine
Lambert, Sarah A. E.
The nuclear pore primes recombination-dependent DNA synthesis at arrested forks by promoting SUMO removal
title The nuclear pore primes recombination-dependent DNA synthesis at arrested forks by promoting SUMO removal
title_full The nuclear pore primes recombination-dependent DNA synthesis at arrested forks by promoting SUMO removal
title_fullStr The nuclear pore primes recombination-dependent DNA synthesis at arrested forks by promoting SUMO removal
title_full_unstemmed The nuclear pore primes recombination-dependent DNA synthesis at arrested forks by promoting SUMO removal
title_short The nuclear pore primes recombination-dependent DNA synthesis at arrested forks by promoting SUMO removal
title_sort nuclear pore primes recombination-dependent dna synthesis at arrested forks by promoting sumo removal
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648084/
https://www.ncbi.nlm.nih.gov/pubmed/33159083
http://dx.doi.org/10.1038/s41467-020-19516-z
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