Excessive Cell Growth Causes Cytoplasm Dilution And Contributes to Senescence.

Cell
Gabriel E NeurohrAngelika Amon

Abstract

Cell size varies greatly between cell types, yet within a specific cell type and growth condition, cell size is narrowly distributed. Why maintenance of a cell-type specific cell size is important remains poorly understood. Here we show that growing budding yeast and primary mammalian cells beyond a certain size impairs gene induction, cell-cycle progression, and cell signaling. These defects are due to the inability of large cells to scale nucleic acid and protein biosynthesis in accordance with cell volume increase, which effectively leads to cytoplasm dilution. We further show that loss of scaling beyond a certain critical size is due to DNA becoming limiting. Based on the observation that senescent cells are large and exhibit many of the phenotypes of large cells, we propose that the range of DNA:cytoplasm ratio that supports optimal cell function is limited and that ratios outside these bounds contribute to aging.

Citations

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Datasets Mentioned

BETA
GSE110704

Methods Mentioned

BETA
flow cytometry
immunoprecipitation
confocal microscopy
protein assay
RNA Seq
environmental stress
ESR
RNASeq
FACS
PCR

Software Mentioned

STAR
ImageJ
Excel
NIS
StarSearch
GSEA
Volocity
element

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