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: Using fixed imaging, we examined the number of centrioles at various time points after IAA treatment. As expected, untreated control cells divided with two centrioles at each spindle pole (Fig. 4, A and B). In contrast, at 1 d after IAA addition, >90% of Plk4AID/AID cells divided with a single centriole at each spindle pole, whereas at days 2 and 3 after IAA addition >65% of cells divided with an asymmetric spindle comprised of an acentriolar pole and a pole containing a single centriole (Fig. 4, A and B). Cell divisions were rarely observed to take place in the absence of centrioles.
Affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.