title: Regulation of Mus81-Eme1 Holliday junction resolvase in response to DNA damage.
abstract: Structure-specific DNA endonucleases have critical roles during DNA replication, repair and recombination, yet they also have the potential for causing genome instability. Controlling these enzymes may be essential to ensure efficient processing of ad hoc substrates and to prevent random, unscheduled processing of other DNA structures, but it is unknown whether structure-specific endonucleases are regulated in response to DNA damage. Here, we uncover DNA damage-induced activation of Mus81-Eme1 Holliday junction resolvase in fission yeast. This new regulation requires both Cdc2(CDK1)- and Rad3(ATR)-dependent phosphorylation of Eme1. Mus81-Eme1 activation prevents gross chromosomal rearrangements in cells lacking the BLM-related DNA helicase Rqh1. We propose that linking Mus81-Eme1 DNA damage-induced activation to cell-cycle progression ensures efficient resolution of Holliday junctions that escape dissolution by Rqh1-TopIII while preventing unnecessary DNA cleavages.
authors.affiliation: Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7258, Inserm-Unité 1068, Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, France.
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Dehé
authors.forename: Stéphane
authors.initials: S
authors.lastname: Coulon
authors.forename: Sarah
authors.initials: S
authors.lastname: Scaglione
authors.forename: Paul
authors.initials: P
authors.lastname: Shanahan
authors.forename: Arato
authors.initials: A
authors.lastname: Takedachi
authors.forename: James A
authors.initials: JA
authors.lastname: Wohlschlegel
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.forename: Bertrand
authors.initials: B
authors.lastname: Llorente
authors.forename: Paul
authors.initials: P
authors.lastname: Russell
authors.forename: Pierre-Henri L
authors.initials: PH
authors.lastname: Gaillard
mesh_terms: D016203:CDC2 Protein Kinase / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D064447:Checkpoint Kinase 2; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004720:Endonucleases / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D045565:Holliday Junction Resolvases / Q000378:metabolism*; D008954:Models, Biological; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012568:Schizosaccharomyces / Q000201:enzymology*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C495865:MUS81 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C456840:rad3 protein, S pombe; D016203:CDC2 Protein Kinase; C469447:cdc2 protein, S pombe; C442837:Eme1 protein, S pombe; D004720:Endonucleases; D045565:Holliday Junction Resolvases