title: Growth rate and cell size modulate the synthesis of, and requirement for, G1-phase cyclins at start.
abstract: In Saccharomyces cerevisiae, commitment to cell cycle progression occurs at Start. Progression past Start requires cell growth and protein synthesis, a minimum cell size, and G(1)-phase cyclins. We examined the relationships among these factors. Rapidly growing cells expressed, and required, dramatically more Cln protein than did slowly growing cells. To clarify the role of cell size, we expressed defined amounts of CLN mRNA in cells of different sizes. When Cln was expressed at nearly physiological levels, a critical threshold of Cln expression was required for cell cycle progression, and this critical threshold varied with both cell size and growth rate: as cells grew larger, they needed less CLN mRNA, but as cells grew faster, they needed more Cln protein. At least in part, large cells had a reduced requirement for CLN mRNA because large cells generated more Cln protein per unit of mRNA than did small cells. When Cln was overexpressed, it was capable of promoting Start rapidly, regardless of cell size or growth rate. In summary, the amount of Cln required for Start depends dramatically on both cell size and growth rate. Large cells generate more Cln1 or Cln2 protein for a given amount of CLN mRNA, suggesting the existence of a novel posttranscriptional size control mechanism.
authors.affiliation: Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, 3601 4th St., Lubbock, TX 79430, USA. brandt.schneider@ttuhsc.edu
authors.forename: Brandt L
authors.initials: BL
authors.lastname: Schneider
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Markwardt
authors.forename: George
authors.initials: G
authors.lastname: Tokiwa
authors.forename: Tom
authors.initials: T
authors.lastname: Volpe
authors.forename: Sangeet
authors.initials: S
authors.lastname: Honey
authors.forename: Bruce
authors.initials: B
authors.lastname: Futcher
mesh_terms: D015153:Blotting, Western; D002453:Cell Cycle; D048429:Cell Size; D016213:Cyclins / Q000096:biosynthesis / Q000378:metabolism*; D016193:G1 Phase; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D006207:Half-Life; D007700:Kinetics; D008954:Models, Biological; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C082719:CLN1 protein, S cerevisiae; C082721:CLN2 protein, S cerevisiae; D016213:Cyclins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins