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: We next examined the chronic effect of Plk4 depletion in RPE1 cells. Although Plk4+/+ cells proliferated normally in the presence of IAA, addition of IAA to Plk4AID/AID cells resulted in a cell cycle arrest 48 h after treatment began (Fig. 3 A). Interphase Plk4AID/AID cells exhibited a dramatic reduction in centriole number by 24 h after IAA addition (Fig. 3 B). Centriole number decreased further by 48 h after Plk4 degradation, giving rise to 22% of cells that lack centrioles. After this time, centriole content changed only slowly, consistent with the fact that the vast majority of cells cease proliferating by 48 h after IAA addition.
Affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.