A new role for Rrm3 in repair of replication-born DNA breakage by sister chromatid recombination

• Published in: PLoS genetics Vol. 13; no. 5; p. e1006781
• Main Authors: Muñoz-Galván, Sandra, García-Rubio, María, Ortega, Pedro, Ruiz, Jose F, Jimeno, Sonia, Pardo, Benjamin, Gómez-González, Belén, Aguilera, Andrés
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05.05.2017; Public Library of Science (PLoS)
• Subjects: Analysis; Biology and life sciences; Cancer cells; Cell cycle; Chromatids - genetics; Chromatin; Chromosomes; Deoxyribonucleic acid; DNA; DNA biosynthesis; DNA Breaks, Double-Stranded; DNA damage; DNA helicase; DNA Helicases - genetics; DNA Helicases - metabolism; DNA mismatch repair; DNA Repair; DNA Replication; Double-strand break repair; Genetic aspects; Genetic recombination; Genomes; Homologous recombination; Homology; Open access; Physical Sciences; Proteins; Recruitment; Replication; Replication fork; Replication forks; Research and Analysis Methods; Ribosomal DNA; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Single-stranded DNA; Sister Chromatid Exchange; Stalling; Transcription; Viability; Yeast
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1006781

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 rrm3Δ 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.