Aneuploid Yeast Strains Exhibit Defects in Cell Growth and Passage Through START

Overview

Journal Mol Biol Cell

Specialties Cell Biology
Molecular Biology

Date 2013 Mar 8

PMID 23468524

Citations 62

Authors

Rebecca R Thorburn

Christian Gonzalez

Gloria A Brar

Stefan Christen

Thomas M Carlile

Nicholas T Ingolia

Uwe Sauer

Jonathan S Weissman

Angelika Amon

Affiliations

Soon will be listed here.

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.

Citing Articles

Strain background interacts with chromosome 7 aneuploidy to determine commensal and virulence phenotypes in .

Mishra A, Solis N, Dietz S, Crouch A, Filler S, Anderson M bioRxiv. 2025; .

PMID: 39896449 PMC: 11785170. DOI: 10.1101/2025.01.23.634449.

UPR deficiency in budding yeast reveals a trade-off between ER folding capacity and maintenance of euploidy.

Bartolutti C, Kim A, Brar G bioRxiv. 2024; .

PMID: 39605714 PMC: 11601577. DOI: 10.1101/2024.11.22.624941.

The response to single-gene duplication implicates translation as a key vulnerability in aneuploid yeast.

Dutcher H, Hose J, Howe H, Rojas J, Gasch A PLoS Genet. 2024; 20(10):e1011454.

PMID: 39453980 PMC: 11540229. DOI: 10.1371/journal.pgen.1011454.

Comparative modeling reveals the molecular determinants of aneuploidy fitness cost in a wild yeast model.

Rojas J, Hose J, Dutcher H, Place M, Wolters J, Hittinger C Cell Genom. 2024; 4(10):100656.

PMID: 39317188 PMC: 11602619. DOI: 10.1016/j.xgen.2024.100656.

The two sides of chromosomal instability: drivers and brakes in cancer.

Hosea R, Hillary S, Naqvi S, Wu S, Kasim V Signal Transduct Target Ther. 2024; 9(1):75.

PMID: 38553459 PMC: 10980778. DOI: 10.1038/s41392-024-01767-7.

References

Ferrezuelo F, Colomina N, Palmisano A, Gari E, Gallego C, Csikasz-Nagy A . The critical size is set at a single-cell level by growth rate to attain homeostasis and adaptation. Nat Commun. 2012; 3:1012. DOI: 10.1038/ncomms2015. View

Hoose S, Rawlings J, Kelly M, Leitch M, Ababneh Q, Robles J . A systematic analysis of cell cycle regulators in yeast reveals that most factors act independently of cell size to control initiation of division. PLoS Genet. 2012; 8(3):e1002590. PMC: 3305459. DOI: 10.1371/journal.pgen.1002590. View

Hinnebusch A . A hierarchy of trans-acting factors modulates translation of an activator of amino acid biosynthetic genes in Saccharomyces cerevisiae. Mol Cell Biol. 1985; 5(9):2349-60. PMC: 366962. DOI: 10.1128/mcb.5.9.2349-2360.1985. View

Mai B, Breeden L . Xbp1, a stress-induced transcriptional repressor of the Saccharomyces cerevisiae Swi4/Mbp1 family. Mol Cell Biol. 1997; 17(11):6491-501. PMC: 232502. DOI: 10.1128/MCB.17.11.6491. View

Ingolia N, Ghaemmaghami S, Newman J, Weissman J . Genome-wide analysis in vivo of translation with nucleotide resolution using ribosome profiling. Science. 2009; 324(5924):218-23. PMC: 2746483. DOI: 10.1126/science.1168978. View

Cross F, Hoek M, McKinney J, Tinkelenberg A . Role of Swi4 in cell cycle regulation of CLN2 expression. Mol Cell Biol. 1994; 14(7):4779-87. PMC: 358851. DOI: 10.1128/mcb.14.7.4779-4787.1994. View

Rowley A, Johnston G, Butler B, Werner-Washburne M, Singer R . Heat shock-mediated cell cycle blockage and G1 cyclin expression in the yeast Saccharomyces cerevisiae. Mol Cell Biol. 1993; 13(2):1034-41. PMC: 358988. DOI: 10.1128/mcb.13.2.1034-1041.1993. View

Verduyn C, Postma E, Scheffers W, van Dijken J . Effect of benzoic acid on metabolic fluxes in yeasts: a continuous-culture study on the regulation of respiration and alcoholic fermentation. Yeast. 1992; 8(7):501-17. DOI: 10.1002/yea.320080703. View

Futcher B . Transcriptional regulatory networks and the yeast cell cycle. Curr Opin Cell Biol. 2002; 14(6):676-83. DOI: 10.1016/s0955-0674(02)00391-5. View

10.

de Bruin R, McDonald W, Kalashnikova T, Yates 3rd J, Wittenberg C . Cln3 activates G1-specific transcription via phosphorylation of the SBF bound repressor Whi5. Cell. 2004; 117(7):887-98. DOI: 10.1016/j.cell.2004.05.025. View

11.

Tyers M, Tokiwa G, Nash R, Futcher B . The Cln3-Cdc28 kinase complex of S. cerevisiae is regulated by proteolysis and phosphorylation. EMBO J. 1992; 11(5):1773-84. PMC: 556635. DOI: 10.1002/j.1460-2075.1992.tb05229.x. View

12.

Brar G, Yassour M, Friedman N, Regev A, Ingolia N, Weissman J . High-resolution view of the yeast meiotic program revealed by ribosome profiling. Science. 2011; 335(6068):552-7. PMC: 3414261. DOI: 10.1126/science.1215110. View

13.

Sheltzer J, Torres E, Dunham M, Amon A . Transcriptional consequences of aneuploidy. Proc Natl Acad Sci U S A. 2012; 109(31):12644-9. PMC: 3411958. DOI: 10.1073/pnas.1209227109. View

14.

Tang Y, Williams B, Siegel J, Amon A . Identification of aneuploidy-selective antiproliferation compounds. Cell. 2011; 144(4):499-512. PMC: 3532042. DOI: 10.1016/j.cell.2011.01.017. View

15.

Fingerman I, Nagaraj V, Norris D, Vershon A . Sfp1 plays a key role in yeast ribosome biogenesis. Eukaryot Cell. 2003; 2(5):1061-8. PMC: 219361. DOI: 10.1128/EC.2.5.1061-1068.2003. View

16.

Segal D, McCoy E . Studies on Down's syndrome in tissue culture. I. Growth rates and protein contents of fibroblast cultures. J Cell Physiol. 1974; 83(1):85-90. DOI: 10.1002/jcp.1040830112. View

17.

Wang H, Carey L, Cai Y, Wijnen H, Futcher B . Recruitment of Cln3 cyclin to promoters controls cell cycle entry via histone deacetylase and other targets. PLoS Biol. 2009; 7(9):e1000189. PMC: 2730028. DOI: 10.1371/journal.pbio.1000189. View

18.

Nash R, Tokiwa G, Anand S, Erickson K, Futcher A . The WHI1+ gene of Saccharomyces cerevisiae tethers cell division to cell size and is a cyclin homolog. EMBO J. 1988; 7(13):4335-46. PMC: 455150. DOI: 10.1002/j.1460-2075.1988.tb03332.x. View

19.

Tyers M, Tokiwa G, Futcher B . Comparison of the Saccharomyces cerevisiae G1 cyclins: Cln3 may be an upstream activator of Cln1, Cln2 and other cyclins. EMBO J. 1993; 12(5):1955-68. PMC: 413417. DOI: 10.1002/j.1460-2075.1993.tb05845.x. View

20.

Niwa O, Tange Y, Kurabayashi A . Growth arrest and chromosome instability in aneuploid yeast. Yeast. 2006; 23(13):937-50. DOI: 10.1002/yea.1411. View