title: Aneuploid yeast strains exhibit defects in cell growth and passage through START.
abstract: Aneuploidy, a chromosome content that is not a multiple of the haploid karyotype, is associated with reduced fitness in all organisms analyzed to date. In budding yeast aneuploidy causes cell proliferation defects, with many different aneuploid strains exhibiting a delay in G1, a cell cycle stage governed by extracellular cues, growth rate, and cell cycle events. Here we characterize this G1 delay. We show that 10 of 14 aneuploid yeast strains exhibit a growth defect during G1. Furthermore, 10 of 14 aneuploid strains display a cell cycle entry delay that correlates with the size of the additional chromosome. This cell cycle entry delay is due to a delayed accumulation of G1 cyclins that can be suppressed by supplying cells with high levels of a G1 cyclin. Our results indicate that aneuploidy frequently interferes with the ability of cells to grow and, as with many other cellular stresses, entry into the cell cycle.
authors.affiliation: David H. Koch Institute for Integrative Cancer Research and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Rebecca R
authors.initials: RR
authors.lastname: Thorburn
authors.forename: Christian
authors.initials: C
authors.lastname: Gonzalez
authors.forename: Gloria A
authors.initials: GA
authors.lastname: Brar
authors.forename: Stefan
authors.initials: S
authors.lastname: Christen
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Carlile
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Ingolia
authors.forename: Uwe
authors.initials: U
authors.lastname: Sauer
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Weissman
authors.forename: Angelika
authors.initials: A
authors.lastname: Amon
mesh_terms: D021581:Active Transport, Cell Nucleus; D000596:Amino Acids / Q000096:biosynthesis; D000782:Aneuploidy; D018244:Chromosomes, Artificial, Yeast / Q000235:genetics; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D055442:Metabolome; D014176:Protein Biosynthesis; D012097:Repressor Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D000596:Amino Acids; C082733:BCK2 protein, S cerevisiae; C082721:CLN2 protein, S cerevisiae; C079895:CLN3 protein, S cerevisiae; D016213:Cyclins; D047908:Intracellular Signaling Peptides and Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C508130:Whi5 protein, S cerevisiae; D018844:Cyclin-Dependent Kinases