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 language | English (US) |
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Pages (from-to) | 1584-1588 |
Number of pages | 5 |
Journal | Genes and Development |
Volume | 14 |
Issue number | 13 |
State | Published - Jul 1 2000 |
Keywords
- 14-3.3σ
- Cell cycle
- Checkpoint
- p21
- p53
ASJC Scopus subject areas
- Genetics
- Developmental Biology