DOI: 10.1101/470013Nov 14, 2018Paper

Cell growth dilutes the cell cycle inhibitor Rb to trigger cell division

BioRxiv : the Preprint Server for Biology
Evgeny ZatulovskiyJan M Skotheim

Abstract

Cell size is fundamental to function in different cell types across the human body because it sets the scale of organelle structures, biosynthesis, and surface transport. Tiny erythrocytes squeeze through capillaries to transport oxygen, while the million-fold larger oocyte divides without growth to form the ~100 cell pre-implantation embryo. Despite the vast size range across cell types, cells of a given type are typically uniform in size likely because cells are able to accurately couple cell growth to division. While some genes whose disruption in mammalian cells affects cell size have been identified, the molecular mechanisms through which cell growth drives cell division have remained elusive. Here, we show that cell growth acts to dilute the cell cycle inhibitor Rb to drive cell cycle progression from G1 to S phase in human cells. In contrast, other G1/S regulators remained at nearly constant concentration. Rb is a stable protein that is synthesized during S and G2 phases in an amount that is independent of cell size. Equal partitioning to daughter cells of chromatin bound Rb then ensures that all cells at birth inherit a similar amount of Rb protein. RB overexpression increased cell size in tissue culture and a mouse can...Continue Reading

Related Concepts

Birth
Blood Capillaries
Cell Cycle
Cell Division
Cell Growth
Enzyme Inhibitors
Erythrocytes
Gene Deletion
Genes
Oocytes

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