Cooperative effects of genes controlling the G2/M checkpoint

Timothy A. Chan, Paul M. Hwang, Heiko Hermeking, Kenneth W. Kinzler, Bert Vogelstein

Research output: Contribution to journalArticlepeer-review

240 Scopus citations

Abstract

It is believed that multiple effectors independently control the checkpoints permitting transitions between cell cycle phases. However, this has not been rigorously demonstrated in mammalian cells. The p53-induced genes p21 and 14-3-3σ are each required for the G2 arrest and allow a specific test of this fundamental tenet. We generated human cells deficient in both p21 and 14-3-3σ and determined whether the double knockout was more sensitive to DNA damage than either single knockout. p21(-/-) 14-3-3σ(-/-) cells were significantly more sensitive to DNA damage or to the exogenous expression of p53 than cells lacking only p21 or only 14-3-3σ. Thus, p21 and 14-3-3σ play distinct but complementary roles in the G2/M checkpoint, and help explain why genes at the nodal points of growth arrest pathways, like p53, are the targets of mutation in cancer cells.

Original languageEnglish (US)
Pages (from-to)1584-1588
Number of pages5
JournalGenes and Development
Volume14
Issue number13
StatePublished - Jul 1 2000

Keywords

  • 14-3.3σ
  • Cell cycle
  • Checkpoint
  • p21
  • p53

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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