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About the Authors:
Sandra Muñoz-Galván
Affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Seville, Spain
María García-Rubio
Affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Seville, Spain
Pedro Ortega
Affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Seville, Spain
Jose F. Ruiz
Affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Seville, Spain
Sonia Jimeno
Affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Seville, Spain
Benjamin Pardo
Current address: Institut de Genetique Humaine, CNRS, Montpellier, France
Affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Seville, Spain
Belén Gómez-González
* E-mail: [email protected] (AA); [email protected] (BGG)
Affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Seville, Spain
Andrés Aguilera
* E-mail: [email protected] (AA); [email protected] (BGG)
Affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Seville, Spain
ORCID http://orcid.org/0000-0003-4782-1714Abstract
Replication forks stall at different DNA obstacles such as those originated by transcription. Fork stalling can lead to DNA double-strand breaks (DSBs) that will be preferentially repaired by homologous recombination when the sister chromatid is available. The Rrm3 helicase is a replisome component that promotes replication upon fork stalling, accumulates at highly transcribed regions and prevents not only transcription-induced replication fork stalling but also transcription-associated hyper-recombination. This led us to explore the possible role of Rrm3 in the repair of DSBs when originating at the passage of the replication fork. Using a mini-HO system that induces mainly single-stranded DNA breaks, we show that rrm3[delta] cells are defective in DSB repair. The defect is clearly seen in sister chromatid recombination, the major repair pathway of replication-born DSBs. Our results indicate that Rrm3 recruitment to replication-born DSBs is crucial for viability, uncovering a new role for Rrm3 in the repair of broken replication forks.
Author summary
DNA replication needs to be precise to ensure cell survival and to avoid genetic instability. Different DNA obstacles, such as those originated by transcription, frequently hamper replication fork progression leading to fork stalling or even fork breakage. This requires the homologous recombination...