title: Aneuploidy and improved growth are coincident but not causal in a yeast cancer model.
abstract: Cancer cells have acquired mutations that alter their growth. Aneuploidy that typify cancer cells are often assumed to contribute to the abnormal growth characteristics. Here we test the idea of a link between aneuploidy and mutations allowing improved growth, using Saccharomyces cerevisiae containing a mcm4 helicase allele that was shown to cause cancer in mice. Yeast bearing this mcm4 allele are prone to undergoing a "hypermutable phase" characterized by a changing karyotype, ultimately yielding progeny with improved growth properties. When such progeny are returned to a normal karyotype by mating, their improved growth remains. Genetic analysis shows their improved growth is due to mutations in just a few loci. In sum, the effects of the mcm4 allele in mice are recapitulated in yeast, and the aneuploidy is not required to maintain improved growth.
authors.affiliation: Department of Molecular Biology and Genetics, College of Agriculture and Life Sciences, Cornell University, Ithaca, New York, USA.
authors.forename: Xin Chenglin
authors.initials: XC
authors.lastname: Li
authors.forename: John C
authors.initials: JC
authors.lastname: Schimenti
authors.forename: Bik K
authors.initials: BK
authors.lastname: Tye
mesh_terms: D000483:Alleles; D000782:Aneuploidy; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016195:G2 Phase; D051379:Mice; D064148:Minichromosome Maintenance Complex Component 4; D009154:Mutation; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; C092802:MCM4 protein, S cerevisiae; D064148:Minichromosome Maintenance Complex Component 4