title: Stress activated protein kinase pathway modulates homologous recombination in fission yeast.
abstract: Rad52 is a key player in homologous recombination (HR), a DNA repair pathway that is dedicated to double strand breaks repair and recovery of perturbed replication forks. Here we show that fission yeast Rad52 homologue is phosphorylated when S phase cells are exposed to ROS inducers such as ultraviolet A radiation or hydrogen peroxide, but not to ultraviolet C or camptothecin. Phosphorylation does not depend on kinases Chk1, Rad3, Tel1 or Cdc2, but depends on a functional stress activated protein kinase (SAPK) pathway and can be partially prevented by anti-oxidant treatment. Indeed, cells lacking Sty1, the major fission yeast MAP kinase of the SAPK pathway, do not display Rad52 phosphorylation and have UVA induced Rad52 foci that persist longer if compared to wild type cells. In addition, spontaneous intrachromosomal HR is diminished in cells lacking Sty1 and, more precisely, gene conversion is affected. Moreover, HR induced by site-specific arrest of replication forks is twice less efficient in cells that do not express Sty1. Importantly, impairing HR by deletion of the gene encoding the recombinase Rhp51 leads to Sty1 dependent Rad52 phosphorylation. Thus, SAPK pathway impinges on early step of HR through phosphorylation of Rad52 in cells challenged by oxidative stress or lacking Rhp51 and is required to promote spontaneous gene conversion and recovery from blocked replication forks.
authors.affiliation: Institut Curie, Centre de Recherche, Orsay, France.
authors.forename: Angela
authors.initials: A
authors.lastname: Bellini
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Girard
authors.forename: Sarah
authors.initials: S
authors.lastname: Lambert
authors.forename: Ludovic
authors.initials: L
authors.lastname: Tessier
authors.forename: Evelyne
authors.initials: E
authors.lastname: Sage
authors.forename: Stefania
authors.initials: S
authors.lastname: Francesconi
mesh_terms: D002166:Camptothecin / Q000494:pharmacology; D004261:DNA Replication; D005785:Gene Conversion; D006360:Heat-Shock Proteins / Q000378:metabolism; D059765:Homologous Recombination / Q000528:radiation effects*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000528:radiation effects*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000528:radiation effects; D051135:Rad51 Recombinase / Q000378:metabolism; D051721:Rad52 DNA Repair and Recombination Protein / Q000378:metabolism; D016196:S Phase; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism; D059004:Topoisomerase I Inhibitors / Q000494:pharmacology; D014466:Ultraviolet Rays
chemical_list: D006360:Heat-Shock Proteins; D016877:Oxidants; C084232:RHP51 protein, S pombe; D051721:Rad52 DNA Repair and Recombination Protein; C519171:SPCC191.01 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; D059004:Topoisomerase I Inhibitors; D006861:Hydrogen Peroxide; D011494:Protein Kinases; D020928:Mitogen-Activated Protein Kinases; C095409:sty1 protein, S pombe; D051135:Rad51 Recombinase; D002166:Camptothecin