title: Defective in mitotic arrest 1 (Dma1) ubiquitin ligase controls G1 cyclin degradation.
abstract: Progression through the G(1) phase of the cell cycle is controlled by diverse cyclin-dependent kinases (CDKs) that might be associated to numerous cyclin isoforms. Given such complexity, regulation of cyclin degradation should be crucial for coordinating progression through the cell cycle. In Saccharomyces cerevisiae, SCF is the only E3 ligase known to date to be involved in G(1) cyclin degradation. Here, we report the design of a genetic screening that uncovered Dma1 as another E3 ligase that targets G(1) cyclins in yeast. We show that the cyclin Pcl1 is ubiquitinated in vitro and in vivo by Dma1, and accordingly, is stabilized in dma1 mutants. We demonstrate that Pcl1 must be phosphorylated by its own CDK to efficiently interact with Dma1 and undergo degradation. A nonphosphorylatable version of Pcl1 accumulates throughout the cell cycle, demonstrating the physiological relevance of the proposed mechanism. Finally, we present evidence that the levels of Pcl1 and Cln2 are independently controlled in response to nutrient availability. This new previously unknown mechanism for G(1) cyclin degradation that we report here could help elucidate the specific roles of the redundant CDK-cyclin complexes in G(1).
authors.affiliation: Departament de Ciències Bàsiques, Universitat Internacional de Catalunya, 08017 Barcelona, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Hernández-Ortega
authors.forename: Samuel
authors.initials: S
authors.lastname: Bru
authors.forename: Natalia
authors.initials: N
authors.lastname: Ricco
authors.forename: Sara
authors.initials: S
authors.lastname: Ramírez
authors.forename: Núria
authors.initials: N
authors.lastname: Casals
authors.forename: Javier
authors.initials: J
authors.lastname: Jiménez
authors.forename: Marta
authors.initials: M
authors.lastname: Isasa
authors.forename: Bernat
authors.initials: B
authors.lastname: Crosas
authors.forename: Josep
authors.initials: J
authors.lastname: Clotet
mesh_terms: D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D056766:Cyclin G1 / Q000737:chemistry* / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods; D008954:Models, Biological; D009154:Mutation; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D053719:Tandem Mass Spectrometry / Q000379:methods; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D056766:Cyclin G1; D016213:Cyclins; C493792:Dma1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C070839:PCL1 protein, S cerevisiae; D012313:RNA; D018844:Cyclin-Dependent Kinases; C058605:PHO85 protein, S cerevisiae; D046988:Proteasome Endopeptidase Complex