A checkpoint-independent mechanism delays entry into mitosis after UV irradiation

J Cell Sci. 2017 Dec 1;130(23):4028-4037. doi: 10.1242/jcs.204693. Epub 2017 Oct 18.

Abstract

When cells are exposed to stress they delay entry into mitosis. The most extensively studied mechanism behind this delay is the DNA-damage-induced G2/M checkpoint. Here, we show the existence of an additional stress-response pathway in Schizosaccharomyces pombe that is independent of the classic ATR/Rad3-dependent checkpoint. This novel mechanism delays entry mitosis independently of the spindle assembly checkpoint and the mitotic kinases Fin1, Ark1 and Plo1. The pathway delays activation of the mitotic cyclin-dependent kinase (CDK) Cdc2 after UV irradiation. Furthermore, we demonstrate that translation of the mitotic cyclin Cdc13 is selectively downregulated after UV irradiation, and we propose that this downregulation of Cdc13 contributes to the delayed activation of Cdc2 and the delayed mitosis.

Keywords: Checkpoint; Cyclin B; G2/M; Selective translation; UV.

MeSH terms

  • CDC2 Protein Kinase / metabolism
  • Cell Cycle Proteins / metabolism*
  • Cyclin-Dependent Kinases / metabolism
  • DNA Damage / physiology*
  • Mitosis / physiology*
  • Phosphorylation
  • Protein Kinases / metabolism
  • Protein Serine-Threonine Kinases / metabolism
  • Schizosaccharomyces / metabolism
  • Schizosaccharomyces pombe Proteins / metabolism
  • Ultraviolet Rays*

Substances

  • Cell Cycle Proteins
  • Schizosaccharomyces pombe Proteins
  • Protein Kinases
  • Protein Serine-Threonine Kinases
  • CDC2 Protein Kinase
  • Cyclin-Dependent Kinases