title: A Whi7-anchored loop controls the G1 Cdk-cyclin complex at start.
abstract: Cells commit to a new cell cycle at Start by activation of the G1 Cdk-cyclin complex which, in turn, triggers a genome-wide transcriptional wave that executes the G1/S transition. In budding yeast, the Cdc28-Cln3 complex is regulated by an ER-retention mechanism that is important for proper cell size control. We have isolated small-cell-size CDC28 mutants showing impaired retention at the ER and premature accumulation of the Cln3 cyclin in the nucleus. The differential interactome of a quintuple Cdc28(wee) mutant pinpointed Whi7, a Whi5 paralog targeted by Cdc28 that associates to the ER in a phosphorylation-dependent manner. Our results demonstrate that the Cln3 cyclin and Whi7 act in a positive feedback loop to release the G1 Cdk-cyclin complex and trigger Start once a critical size has been reached, thus uncovering a key nonlinear mechanism at the earliest known events of cell-cycle entry.
authors.affiliation: Molecular Biology Institute of Barcelona (IBMB-CSIC), 08028 Barcelona, Catalonia, Spain.
authors.forename: Galal
authors.initials: G
authors.lastname: Yahya
authors.affiliation: Molecular Biology Institute of Barcelona (IBMB-CSIC), 08028 Barcelona, Catalonia, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Parisi
authors.affiliation: Molecular Biology Institute of Barcelona (IBMB-CSIC), 08028 Barcelona, Catalonia, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Flores
authors.affiliation: Molecular Biology Institute of Barcelona (IBMB-CSIC), 08028 Barcelona, Catalonia, Spain.
authors.forename: Carme
authors.initials: C
authors.lastname: Gallego
authors.affiliation: Molecular Biology Institute of Barcelona (IBMB-CSIC), 08028 Barcelona, Catalonia, Spain. Electronic address: marti.aldea@ibmb.csic.es.
authors.forename: Martí
authors.initials: M
authors.lastname: Aldea
mesh_terms: D017489:CDC28 Protein Kinase, S cerevisiae / Q000235:genetics / Q000378:metabolism*; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism*; D016193:G1 Phase / Q000502:physiology*; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C079895:CLN3 protein, S cerevisiae; D016213:Cyclins; D029701:Saccharomyces cerevisiae Proteins; D017489:CDC28 Protein Kinase, S cerevisiae