title: A systematic analysis of cell cycle regulators in yeast reveals that most factors act independently of cell size to control initiation of division.
abstract: Upstream events that trigger initiation of cell division, at a point called START in yeast, determine the overall rates of cell proliferation. The identity and complete sequence of those events remain unknown. Previous studies relied mainly on cell size changes to identify systematically genes required for the timely completion of START. Here, we evaluated panels of non-essential single gene deletion strains for altered DNA content by flow cytometry. This analysis revealed that most gene deletions that altered cell cycle progression did not change cell size. Our results highlight a strong requirement for ribosomal biogenesis and protein synthesis for initiation of cell division. We also identified numerous factors that have not been previously implicated in cell cycle control mechanisms. We found that CBS, which catalyzes the synthesis of cystathionine from serine and homocysteine, advances START in two ways: by promoting cell growth, which requires CBS's catalytic activity, and by a separate function, which does not require CBS's catalytic activity. CBS defects cause disease in humans, and in animals CBS has vital, non-catalytic, unknown roles. Hence, our results may be relevant for human biology. Taken together, these findings significantly expand the range of factors required for the timely initiation of cell division. The systematic identification of non-essential regulators of cell division we describe will be a valuable resource for analysis of cell cycle progression in yeast and other organisms.
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Hoose
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Rawlings
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Kelly
authors.forename: M Camille
authors.initials: MC
authors.lastname: Leitch
authors.forename: Qotaiba O
authors.initials: QO
authors.lastname: Ababneh
authors.forename: Juan P
authors.initials: JP
authors.lastname: Robles
authors.forename: David
authors.initials: D
authors.lastname: Taylor
authors.forename: Evelyn M
authors.initials: EM
authors.lastname: Hoover
authors.forename: Bethel
authors.initials: B
authors.lastname: Hailu
authors.forename: Kayla A
authors.initials: KA
authors.lastname: McEnery
authors.forename: S Sabina
authors.initials: SS
authors.lastname: Downing
authors.forename: Deepika
authors.initials: D
authors.lastname: Kaushal
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.forename: Alex
authors.initials: A
authors.lastname: Rife
authors.forename: Kirtan A
authors.initials: KA
authors.lastname: Brahmbhatt
authors.forename: Roger
authors.initials: R
authors.lastname: Smith
authors.forename: Michael
authors.initials: M
authors.lastname: Polymenis
mesh_terms: D002455:Cell Division / Q000235:genetics*; D049109:Cell Proliferation; D048429:Cell Size; D004247:DNA / Q000032:analysis; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics*; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks; D006720:Homozygote; D012270:Ribosomes / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development
chemical_list: D005656:Fungal Proteins; D004247:DNA