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

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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