title: Spatially distinct functions of Clb2 in the DNA damage response.
abstract: In budding yeast four mitotic cyclins (Clb1-4) cooperate in a partially redundant manner to bring about M-phase specific events, including the apical isotropic switch that ends polarized bud growth initiated at bud emergence. How exactly this morphogenetic transition is regulated by mitotic CDKs remains poorly understood. We have taken advantage of the isotropic bud growth that prevails in cells responding to DNA damage to unravel the contribution of mitotic cyclins in this cellular context. We find that clb2∆, in contrast to the other mitotic cyclin mutants, inappropriately respond to the presence of DNA damage. This aberrant response is characterized by a Cdc42- and Bni1-dependent but Cln-independent resumption of polarized bud growth after a brief period of actin depolarization. Biochemical and genetic evidence is presented that formally excludes the possibility of indirect effects due for instance to unrestrained APC activity, untimely mitotic exit or Swe1-mediated CDK inhibition. Importantly, our data demonstrate that in order to maintain the characteristic dumbbell arrest phenotype upon checkpoint activation Clb2 needs to be efficiently exported into the cytoplasm. We propose that the inhibition of mitotic cyclin destruction by the DNA damage checkpoint pathway leads to a buildup of Clb2 in the cytoplasm where this cyclin can stabilize the apical isotropic switch throughout a G 2/M checkpoint arrest. Our study also unveils an essential role of nuclear Clb2 in both survival and adaptation to the DNA damage checkpoint, illustrating a spatially distinct dual function of this mitotic cyclin in the response to DNA damage.
authors.affiliation: CNRS; UPR9027; Laboratoire d'Ingénierie des Systèmes Macromoléculaires; Marseille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Machu
authors.affiliation: CNRS; UPR9027; Laboratoire d'Ingénierie des Systèmes Macromoléculaires; Marseille, France; CNRS; UPR3081; Instabilité du Génome et Cancérogenèse; Marseille, France.
authors.forename: Raïssa
authors.initials: R
authors.lastname: Eluère
authors.affiliation: CNRS; UPR9027; Laboratoire d'Ingénierie des Systèmes Macromoléculaires; Marseille, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Signon
authors.affiliation: CNRS; UPR9027; Laboratoire d'Ingénierie des Systèmes Macromoléculaires; Marseille, France; CNRS; UPR3081; Instabilité du Génome et Cancérogenèse; Marseille, France.
authors.forename: Marie-Noëlle
authors.initials: MN
authors.lastname: Simon
authors.affiliation: CNRS; UPR9027; Laboratoire d'Ingénierie des Systèmes Macromoléculaires; Marseille, France; CNRS; UPR3081; Instabilité du Génome et Cancérogenèse; Marseille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: de La Roche Saint-André
authors.affiliation: CNRS; UPR9027; Laboratoire d'Ingénierie des Systèmes Macromoléculaires; Marseille, France; CNRS; UPR3081; Instabilité du Génome et Cancérogenèse; Marseille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Bailly
mesh_terms: D000199:Actins / Q000378:metabolism; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D059565:G2 Phase Cell Cycle Checkpoints; D008840:Microfilament Proteins / Q000378:metabolism; D008938:Mitosis; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae / Q000378:metabolism
chemical_list: D000199:Actins; C105191:Bni1 protein, S cerevisiae; C093749:CLB2 protein, S cerevisiae; D019926:Cyclin B; D008840:Microfilament Proteins; D029701:Saccharomyces cerevisiae Proteins; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae
keywords: CDK; Clb2; DNA damage; checkpoint; morphogenesis