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: In vertebrate somatic cells, de novo centriole assembly is initiated after the eradication of the existing centrioles by laser ablation or microsurgery (Khodjakov et al., 2002; La Terra et al., 2005; Uetake et al., 2007). In this case a variable number of de novo centrioles are spontaneously generated. We therefore examined the effect of restoring endogenous Plk4 levels in acentriolar cells. Endogenous Plk4 levels returned to normal within 12 h of IAA washout (Fig. 6 A) and promoted the penetrant formation of de novo centrioles: by 2 d after IAA washout, de novo centriole assembly occurred in 74% of cells and increased to >95% of cells by 4 d after IAA removal (Fig. 6 B and Fig. S4 H). Knockdown of the cartwheel component STIL prevented de novo centriole assembly, suggesting that, similar to canonical centriole duplication, de novo centrioles assemble through a cartwheel-dependent mechanism (Fig. 6 C). Collectively, these data show that Plk4 levels are rate limiting for both canonical and de novo centriole assembly.
Affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.