title: Kin3 protein, a NIMA-related kinase of Saccharomyces cerevisiae, is involved in DNA adduct damage response.
abstract: Kin3 is a nonessential serine/threonine protein kinase of the budding yeast Saccharomyces cerevisiae with unknown cellular role. It is an ortholog of the Aspergillus nidulans protein kinase NIMA (Never-In Mitosis, gene A), which is involved in the regulation of G2/M phase progression, DNA damage response and mitosis. The aim of this study was to determine whether Kin3 is required for proper checkpoint activation and DNA repair. Here we show that KIN3 gene deficient cells present sensitivity and fail to arrest properly at G2/M-phase checkpoint in response to the DNA damage inducing agents MMS, cisplatin, doxorubicin and nitrogen mustard, suggesting that Kin3 can be involved in DNA strand breaks recognition or signaling. In addition, there is an increase in KIN3 gene expression in response to the mutagenic treatment, which was confirmed by the increase of Kin3 protein. We also showed that co-treatment with caffeine induces a slight increase in the susceptibility to genotoxic agents in kin3 cells and abolishes KIN3 gene expression in wild-type strain, suggesting that Kin3p can play a role in Tel1/Mec1-dependent pathway activation induced after genotoxic stress. These data provide the first evidence of the involvement of S. cerevisiae Kin3 in the DNA damage response.
authors.affiliation: Department of Biophysics/Biotechnology Center, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Dinara J
authors.initials: DJ
authors.lastname: Moura
authors.forename: Bruna
authors.initials: B
authors.lastname: Castilhos
authors.forename: Bruna F
authors.initials: BF
authors.lastname: Immich
authors.forename: Andrés D
authors.initials: AD
authors.lastname: Cañedo
authors.forename: João A P
authors.initials: JA
authors.lastname: Henriques
authors.forename: Guido
authors.initials: G
authors.lastname: Lenz
authors.forename: Jenifer
authors.initials: J
authors.lastname: Saffi
mesh_terms: D002110:Caffeine / Q000494:pharmacology; D002455:Cell Division; D002945:Cisplatin / Q000494:pharmacology; D018736:DNA Adducts / Q000737:chemistry* / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004317:Doxorubicin / Q000494:pharmacology; D016195:G2 Phase; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008466:Mechlorethamine / Q000494:pharmacology; D008938:Mitosis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism* / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction
chemical_list: D018736:DNA Adducts; D047908:Intracellular Signaling Peptides and Proteins; D029701:Saccharomyces cerevisiae Proteins; D002110:Caffeine; D008466:Mechlorethamine; D004317:Doxorubicin; C075981:KIN3 protein, S cerevisiae; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C513623:TEL1 protein, S cerevisiae; D002945:Cisplatin