抄録
p53 tumor suppressor has been documented to be involved in maintaining stability of the genome through either cell cycle arrest or apoptosis. Recently, the regulation of DNA repair by p53 tumor suppressor has been an emerging important topic in the field of radiation research and oncology, largely distinct and separable from more-studied cell cycle arrest and apoptosis response regulated by p53 (JBC 2005). The crucial role of p53 and its downstream gene Gadd45 in nucleotide excision repair (NER) of DNA damage induced by UV or industrial mutagens has been shown (MCB 2000), but much of its detailed mechanism remains to be elucidated. Moreover, p53 and its downstream gene DNA polymerase beta also participate in base excision repair (BER) of DNA damage induced by free radicals or alkylating mutagens (Cancer Research 2003, Oncogene 2002b), still at an early stage of investigation. Indeed, we demonstrated the relevance of redox factor (ref1) in the mechanism of p53 activation by the reduction of p53 protein under the treatment of selenomethionine (SeMet) (PNAS 2002, Oncogene 2002a). In addition, we found that SeMet also protects cells exposed to ionizing radiation (IR) as well as to UV. Furthermore, transcription activity of p53 was decreased in ref-1 mutant cells under SeMet, suggesting that the redox status of p53 might have protective effects against IR exposue. In conclusion, p53-mediated DNA repair under redox signaling modulation would be an emerging field in radiation research for the cancer prevention and therapy.
