Disruption of ribosome biogenesis triggers a p21/p53-mediated cell cycle checkpoint

Cell cycle entry requires a dramatic increase in protein production. In order to cope with
this demand, the cell must upregulate ribosome biogenesis. Given that ribosome
biogenesis is the most energy-consuming anabolic process in a growing cell, and that
changes in cellular ribosome content can alter the genetic program, we hypothesized
that control mechanisms must exist to synchronize ribosome biogenesis and cell cycle
progression. Here I report on a novel cell cycle checkpoint which is activated on the
disruption of ribosome biogenesis and blocks cell cycle progression. Our studies, both
in vitro and in vivo, show p21 and p53 as key mediators of this response.