2026-06-14T02:29:48Zhttps://repisalud.isciii.es/rest/oai/request

oai: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

00925njm 22002777a 4500 dc Muñoz, Sergio author Blanco-Romero, Elena author Gonzalez-Acosta, Daniel author Rodriguez-Acebes, Sara author Megías, Diego author Lopes, Massimo author Mendez, Juan author 2024-03 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. 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 DNA Replication Fork Progression MRE11 RAD51 Re-replication RAD51 restricts DNA over-replication from re-activated origins