title: Cell cycle population effects in perturbation studies.
abstract: Growth condition perturbation or gene function disruption are commonly used strategies to study cellular systems. Although it is widely appreciated that such experiments may involve indirect effects, these frequently remain uncharacterized. Here, analysis of functionally unrelated Saccharyomyces cerevisiae deletion strains reveals a common gene expression signature. One property shared by these strains is slower growth, with increased presence of the signature in more slowly growing strains. The slow growth signature is highly similar to the environmental stress response (ESR), an expression response common to diverse environmental perturbations. Both environmental and genetic perturbations result in growth rate changes. These are accompanied by a change in the distribution of cells over different cell cycle phases. Rather than representing a direct expression response in single cells, both the slow growth signature and ESR mainly reflect a redistribution of cells over different cell cycle phases, primarily characterized by an increase in the G1 population. The findings have implications for any study of perturbation that is accompanied by growth rate changes. Strategies to counter these effects are presented and discussed.
authors: Molecular Cancer Research, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Eoghan
authors: E
authors: O'Duibhir
authors: Molecular Cancer Research, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Philip
authors: P
authors: Lijnzaad
authors: Molecular Cancer Research, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Joris J
authors: JJ
authors: Benschop
authors: Molecular Cancer Research, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Tineke L
authors: TL
authors: Lenstra
authors: Molecular Cancer Research, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Dik
authors: D
authors: van Leenen
authors: Molecular Cancer Research, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Marian J A
authors: MJ
authors: Groot Koerkamp
authors: Molecular Cancer Research, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Thanasis
authors: T
authors: Margaritis
authors: Molecular Cancer Research, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Mariel O
authors: MO
authors: Brok
authors: Molecular Cancer Research, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Patrick
authors: P
authors: Kemmeren
authors: Molecular Cancer Research, University Medical Center Utrecht, Utrecht, the Netherlands f.c.p.holstege@umcutrecht.nl.
authors: Frank C P
authors: FC
authors: Holstege
mesh_terms: D002453:Cell Cycle; D003470:Culture Media; D030541:Databases, Genetic; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D012441:Saccharomyces cerevisiae / Q000145:classification / Q000166:cytology / Q000235:genetics* / Q000254:growth & development*; D013312:Stress, Physiological
chemical_list: D003470:Culture Media
keywords: environmental stress response; gene deletion; gene expression; genome‐wide transcription; growth rate