Ribosome biogenesis is an energy consuming process which takes place mainly in 
the nucleolus. By producing ribosomes to fuel protein synthesis, it is tightly 
connected with cell growth and cell cycle control. Perturbation of ribosome 
biogenesis leads to the activation of p53 tumor suppressor protein promoting 
processes like cell cycle arrest, apoptosis or senescence. This ribosome 
biogenesis stress pathway activates p53 through sequestration of MDM2 by a 
subset of ribosomal proteins (RPs), thereby stabilizing p53. Here, we identify 
human HEATR1, as a nucleolar protein which positively regulates ribosomal RNA 
(rRNA) synthesis. Downregulation of HEATR1 resulted in cell cycle arrest in a 
manner dependent on p53. Moreover, depletion of HEATR1 also caused disruption of 
nucleolar structure and activated the ribosomal biogenesis stress pathway - RPL5 
/ RPL11 dependent stabilization and activation of p53. These findings reveal an 
important role for HEATR1 in ribosome biogenesis and further support the concept 
that perturbation of ribosome biosynthesis results in p53-dependent cell cycle 
checkpoint activation, with implications for human pathologies including cancer.