2026-06-14T02:29:50Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/189992025-02-27T17:42:53Zcom_20.500.12105_2173com_20.500.12105_2051com_20.500.12105_2052col_20.500.12105_19597col_20.500.12105_25179
Repisalud
author
Muñoz, Sergio
author
Blanco-Romero, Elena
author
Gonzalez-Acosta, Daniel
author
Rodriguez-Acebes, Sara
author
Megías, Diego
author
Lopes, Massimo
author
Mendez, Juan
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Amigos CNIO
funder
Agencia Estatal de Investigación (España)
funder
Ministerio de Ciencia e Innovación (España)
funder
European Molecular Biology Organization
funder
Swiss National Science Foundation
2024-03-19T07:32:08Z
2024-03-19T07:32:08Z
2024-03
EMBO J. 2024 Mar;43(6):1043-1064.
10.1038/s44318-024-00038-z
1460-2075
The EMBO journal
38360996
http://hdl.handle.net/20.500.12105/18999
Eukaryotic cells rely on several mechanisms to ensure that the genome is duplicated precisely once in each cell division cycle, preventing DNA over-replication and genomic instability. Most of these mechanisms limit the activity of origin licensing proteins to prevent the reactivation of origins that have already been used. Here, we have investigated whether additional controls restrict the extension of re-replicated DNA in the event of origin re-activation. In a genetic screening in cells forced to re-activate origins, we found that re-replication is limited by RAD51 and enhanced by FBH1, a RAD51 antagonist. In the presence of chromatin-bound RAD51, forks stemming from re-fired origins are slowed down, leading to frequent events of fork reversal. Eventual re-initiation of DNA synthesis mediated by PRIMPOL creates ssDNA gaps that facilitate the partial elimination of re-duplicated DNA by MRE11 exonuclease. In the absence of RAD51, these controls are abrogated and re-replication forks progress much longer than in normal conditions. Our study uncovers a safeguard mechanism to protect genome stability in the event of origin reactivation.
eng
DNA Replication
Fork Progression
MRE11
RAD51
Re-replication
RAD51 restricts DNA over-replication from re-activated origins
research article
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URL
https://repisalud.isciii.es/bitstreams/781d4e30-08dd-41a6-bce9-653f835dcd85/download
File
MD5
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application/pdf
RAD51_Restricts_DNA_Over_2024.pdf
URL
https://repisalud.isciii.es/bitstreams/e4345c48-bc38-49eb-8d71-a34182f5a675/download
File
MD5
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text/plain
RAD51_Restricts_DNA_Over_2024.pdf.txt