TY - JOUR
T1 - P53 protects against genome instability following centriole duplication failure
AU - Lambrus, Bramwell G.
AU - Uetake, Yumi
AU - Clutario, Kevin M.
AU - Daggubati, Vikas
AU - Snyder, Michael
AU - Sluder, Greenfield
AU - Holland, Andrew J.
N1 - Publisher Copyright:
© 2015 Lambrus et al.
PY - 2015
Y1 - 2015
N2 - Centriole function has been difficult to study because of a lack of specific tools that allow persistent and reversible centriole depletion. Here we combined gene targeting with an auxin-inducible degradation system to achieve rapid, titratable, and reversible control of Polo-like kinase 4 (Plk4), a master regulator of centriole biogenesis. Depletion of Plk4 led to a failure of centriole duplication that produced an irreversible cell cycle arrest within a few divisions. This arrest was not a result of a prolonged mitosis, chromosome segregation errors, or cytokinesis failure. 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.
AB - Centriole function has been difficult to study because of a lack of specific tools that allow persistent and reversible centriole depletion. Here we combined gene targeting with an auxin-inducible degradation system to achieve rapid, titratable, and reversible control of Polo-like kinase 4 (Plk4), a master regulator of centriole biogenesis. Depletion of Plk4 led to a failure of centriole duplication that produced an irreversible cell cycle arrest within a few divisions. This arrest was not a result of a prolonged mitosis, chromosome segregation errors, or cytokinesis failure. 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.
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U2 - 10.1083/jcb.201502089
DO - 10.1083/jcb.201502089
M3 - Article
C2 - 26150389
AN - SCOPUS:84942293631
SN - 0021-9525
VL - 210
SP - 63
EP - 77
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 1
ER -