DNA-Repair Role of p53

Abstract

The transcription factor p53 not only regulates cell-cycle arrest and apoptosis, but Tanaka et al. now show a mechanism by which it can regulate DNA repair as well and thereby maintain genomic stability. The authors have identified a new gene target of p53 called p53-inducible ribonucleotide reductase small subunit 2, or p53R2. The encoded protein is similar to the R2 subunit of an enzyme that catalyzes the production of deoxyribonucleotide trisphosphates (dNTPs). Expression and genome repair activity of p53R2 were induced, in a p53-dependent manner, when cells were exposed to DNA-damaging agents. In p53-deficient cells, p53R2 expression caused cell-cycle arrest and prevented cell death in response to such agents. Unlike R2, which is found in the cytoplasm, p53R2 is found in the nucleus. The authors propose that the cytoplasmic pool of dNTPs may be utilized during DNA replication, but DNA repair within the damaged nuclei of arrested cells may require a source closer to the damaged site. Thus, an important aspect of the p53-dependent DNA-repair pathway appears to be the direct regulation of dNTP synthesis in the nucleus by p53R2.Tanaka, H., Arakawa, H., Yamaguchi, T., Shiraishi, K., Fukuda, S., Matsui, K., Takei, Y., and Nakamura, Y. (2000) A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage. Nature 404: 42-49.[Online Journal]