p53 protects against genome instability following centriole duplication failure.
Bottom Line: Depleting p53 allowed cells that fail centriole duplication to proliferate indefinitely.Washout of auxin and restoration of endogenous Plk4 levels in cells that lack centrioles led to the penetrant formation of de novo centrioles that gained the ability to organize microtubules and duplicate.In summary, we uncover a p53-dependent surveillance mechanism that protects against genome instability by preventing cell growth after centriole duplication failure.
Affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.Show MeSH
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Mentions: To examine whether treatment with IAA leads to the expected failure of centriole duplication, we assessed centriole number in cells undergoing mitosis one cell cycle (30 h) after IAA addition. In untreated Plk4AID/AID cells, centriole duplication occurred successfully in >90% of cells (0 µM IAA; Fig. 2, A and B). In contrast, IAA addition caused a failure of centriole duplication in >90% of Plk4AID/AID cells (500 µM IAA; Fig. 2, A and B). We conclude that Plk4AID/AID cells offer a new tool to achieve rapid and reversible depletion of endogenous Plk4.
Affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.