A ribonucleotide reductase gene is a transcriptional target of p53 and p73

Many p53-inducible genes have been identified that might play a role in med iating the various downstream activities of p53, We have identified a close relative of ribonucleotide reductase, recently named p53R2, as a p53-induc ible gene, and show that this gene is activated by several stress signals t hat activate a p53 response, including DNA damaging agents and p14(ARF), p5 3R2 expression was induced by p53 mutants that are defective for the activa tion of apoptosis, but retain cell cycle arrest function, although no induc tion of p53R2 was seen in response to p21(WAF1/CIP1)-mediated cell cycle ar rest. Several isoforms of the p53 family member p73 were also shown to indu ce p53R2 expression. Transient ectopic expression of either wild type p53R2 or p53R2 targeted to the nucleus, did not significantly alter cell cycle p rogression in unstressed cells, The identification of this gene as a p53 ta rget supports a direct role for p53 in DNA repair, in addition to inhibitio n of growth of damaged cells.