Aneuploid yeast strains exhibit defects in cell growth and passage through START

Mol Biol Cell. 2013 May;24(9):1274-89. doi: 10.1091/mbc.E12-07-0520. Epub 2013 Mar 6.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Amino Acids / biosynthesis
  • Aneuploidy*
  • Chromosomes, Artificial, Yeast / genetics
  • Cyclin-Dependent Kinases / metabolism
  • Cyclins / genetics
  • Cyclins / metabolism
  • G1 Phase Cell Cycle Checkpoints*
  • Gene Expression Regulation, Fungal
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Metabolome
  • Protein Biosynthesis
  • Repressor Proteins / metabolism
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Signal Transduction
  • Transcription, Genetic

Substances

  • Amino Acids
  • BCK2 protein, S cerevisiae
  • CLN2 protein, S cerevisiae
  • CLN3 protein, S cerevisiae
  • Cyclins
  • Intracellular Signaling Peptides and Proteins
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • Whi5 protein, S cerevisiae
  • Cyclin-Dependent Kinases