The Nuclear-to-Cytoplasmic Ratio: Coupling DNA Content to Cell Size, Cell Cycle, and Biosynthetic Capacity

Annu Rev Genet. 2022 Nov 30:56:165-185. doi: 10.1146/annurev-genet-080320-030537. Epub 2022 Aug 17.

Abstract

Though cell size varies between different cells and across species, the nuclear-to-cytoplasmic (N/C) ratio is largely maintained across species and within cell types. A cell maintains a relatively constant N/C ratio by coupling DNA content, nuclear size, and cell size. We explore how cells couple cell division and growth to DNA content. In some cases, cells use DNA as a molecular yardstick to control the availability of cell cycle regulators. In other cases, DNA sets a limit for biosynthetic capacity. Developmentally programmed variations in the N/C ratio for a given cell type suggest that a specific N/C ratio is required to respond to given physiological demands. Recent observations connecting decreased N/C ratios with cellular senescence indicate that maintaining the proper N/C ratio is essential for proper cellular functioning. Together, these findings suggest a causative, not simply correlative, role for the N/C ratio in regulating cell growth and cell cycle progression.

Keywords: DNA-to-cytoplasmic ratio; biosynthetic activity; cell cycle; cell size; nuclear-to-cytoplasmic ratio; polyploidy.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Cycle / genetics
  • Cell Division / genetics
  • Cell Size
  • Cytoplasm / genetics
  • Ploidies*