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RAD52 prevents accumulation of Polα-dependent replication gaps at perturbed replication forks in human cells
Replication gaps can arise as a consequence of perturbed DNA replication and their accumulation might undermine the stability of the genome. Loss of RAD52, a protein involved in the regulation of fork reversal, promotes accumulation of parental ssDNA gaps during replication perturbation. Here, we de...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10120653/ https://www.ncbi.nlm.nih.gov/pubmed/37090680 http://dx.doi.org/10.1101/2023.04.12.536536 |
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author | Di Biagi, Ludovica Malacaria, Eva Aiello, Francesca Antonella Valenzisi, Pasquale Marozzi, Giorgia Franchitto, Annapaola Pichierri, Pietro |
author_facet | Di Biagi, Ludovica Malacaria, Eva Aiello, Francesca Antonella Valenzisi, Pasquale Marozzi, Giorgia Franchitto, Annapaola Pichierri, Pietro |
author_sort | Di Biagi, Ludovica |
collection | PubMed |
description | Replication gaps can arise as a consequence of perturbed DNA replication and their accumulation might undermine the stability of the genome. Loss of RAD52, a protein involved in the regulation of fork reversal, promotes accumulation of parental ssDNA gaps during replication perturbation. Here, we demonstrate that this is due to the engagement of Polα downstream of the extensive degradation of perturbed replication forks after their reversal, and is not dependent on PrimPol. Polα is hyper-recruited at parental ssDNA in the absence of RAD52, and this recruitment is dependent on fork reversal enzymes and RAD51. Of note, we report that the interaction between Polα and RAD51 is stimulated by RAD52 inhibition, and Polα-dependent gap accumulation requires nucleation of RAD51 suggesting that it occurs downstream strand invasion. Altogether, our data indicate that RAD51-Polα-dependent repriming is essential to promote fork restart and limit DNA damage accumulation when RAD52 function is disabled. |
format | Online Article Text |
id | pubmed-10120653 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-101206532023-04-22 RAD52 prevents accumulation of Polα-dependent replication gaps at perturbed replication forks in human cells Di Biagi, Ludovica Malacaria, Eva Aiello, Francesca Antonella Valenzisi, Pasquale Marozzi, Giorgia Franchitto, Annapaola Pichierri, Pietro bioRxiv Article Replication gaps can arise as a consequence of perturbed DNA replication and their accumulation might undermine the stability of the genome. Loss of RAD52, a protein involved in the regulation of fork reversal, promotes accumulation of parental ssDNA gaps during replication perturbation. Here, we demonstrate that this is due to the engagement of Polα downstream of the extensive degradation of perturbed replication forks after their reversal, and is not dependent on PrimPol. Polα is hyper-recruited at parental ssDNA in the absence of RAD52, and this recruitment is dependent on fork reversal enzymes and RAD51. Of note, we report that the interaction between Polα and RAD51 is stimulated by RAD52 inhibition, and Polα-dependent gap accumulation requires nucleation of RAD51 suggesting that it occurs downstream strand invasion. Altogether, our data indicate that RAD51-Polα-dependent repriming is essential to promote fork restart and limit DNA damage accumulation when RAD52 function is disabled. Cold Spring Harbor Laboratory 2023-04-12 /pmc/articles/PMC10120653/ /pubmed/37090680 http://dx.doi.org/10.1101/2023.04.12.536536 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Di Biagi, Ludovica Malacaria, Eva Aiello, Francesca Antonella Valenzisi, Pasquale Marozzi, Giorgia Franchitto, Annapaola Pichierri, Pietro RAD52 prevents accumulation of Polα-dependent replication gaps at perturbed replication forks in human cells |
title | RAD52 prevents accumulation of Polα-dependent replication gaps at perturbed replication forks in human cells |
title_full | RAD52 prevents accumulation of Polα-dependent replication gaps at perturbed replication forks in human cells |
title_fullStr | RAD52 prevents accumulation of Polα-dependent replication gaps at perturbed replication forks in human cells |
title_full_unstemmed | RAD52 prevents accumulation of Polα-dependent replication gaps at perturbed replication forks in human cells |
title_short | RAD52 prevents accumulation of Polα-dependent replication gaps at perturbed replication forks in human cells |
title_sort | rad52 prevents accumulation of polα-dependent replication gaps at perturbed replication forks in human cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10120653/ https://www.ncbi.nlm.nih.gov/pubmed/37090680 http://dx.doi.org/10.1101/2023.04.12.536536 |
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