title: Protein kinase C controls activation of the DNA integrity checkpoint.
abstract: The protein kinase C (PKC) superfamily plays key regulatory roles in numerous cellular processes. Saccharomyces cerevisiae contains a single PKC, Pkc1, whose main function is cell wall integrity maintenance. In this work, we connect the Pkc1 protein to the maintenance of genome integrity in response to genotoxic stresses. Pkc1 and its kinase activity are necessary for the phosphorylation of checkpoint kinase Rad53, histone H2A and Xrs2 protein after deoxyribonucleic acid (DNA) damage, indicating that Pkc1 is required for activation of checkpoint kinases Mec1 and Tel1. Furthermore, Pkc1 electrophoretic mobility is delayed after inducing DNA damage, which reflects that Pkc1 is post-translationally modified. This modification is a phosphorylation event mediated by Tel1. The expression of different mammalian PKC isoforms at the endogenous level in yeast pkc1 mutant cells revealed that PKCδ is able to activate the DNA integrity checkpoint. Finally, downregulation of PKCδ activity in HeLa cells caused a defective activation of checkpoint kinase Chk2 when DNA damage was induced. Our results indicate that the control of the DNA integrity checkpoint by PKC is a mechanism conserved from yeast to humans.
authors.affiliation: Departament de Bioquímica i Biologia Molecular. Universitat de València, 46100 Burjassot (Valencia), Spain.
authors.forename: María
authors.initials: M
authors.lastname: Soriano-Carot
authors.affiliation: Departament de Bioquímica i Biologia Molecular. Universitat de València, 46100 Burjassot (Valencia), Spain.
authors.forename: Inma
authors.initials: I
authors.lastname: Quilis
authors.affiliation: Departament de Bioquímica i Biologia Molecular. Universitat de València, 46100 Burjassot (Valencia), Spain.
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Bañó
authors.affiliation: Departament de Bioquímica i Biologia Molecular. Universitat de València, 46100 Burjassot (Valencia), Spain jcigual@uv.es.
authors.forename: J Carlos
authors.initials: JC
authors.lastname: Igual
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D064447:Checkpoint Kinase 2 / Q000378:metabolism; D004249:DNA Damage; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D009153:Mutagens / Q000633:toxicity; D009154:Mutation; D011493:Protein Kinase C / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051745:Protein Kinase C-delta / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009153:Mutagens; D029701:Saccharomyces cerevisiae Proteins; D064447:Checkpoint Kinase 2; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C513623:TEL1 protein, S cerevisiae; C490702:PKC1 protein, S cerevisiae; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; C067022:RAD53 protein, S cerevisiae