DNA-DAMAGE INCREASES THE LEVELS OF MDM2 MESSENGER-RNA IN WTP53 HUMAN-CELLS

Damage to chromosomal DNA increases the levels of the transcriptional regulatory protein p53. We have investigated how the MDM2 protein, whi ch binds to p53 and inactivates its transcriptional activity, may be c ontrolled following DNA damage. Irradiation of human GM2149 fibroblast cells causes an increase in MDM2 mRNA levels within 1 h, and levels r emain elevated for at least 8 h. The induction of MDM2 mRNA following irradiation is not blocked by inhibitors of protein synthesis and can be detected after doses of 2-5 Gy. In ataxia telangiectasia cells or c ells where p53 is mutated/deleted, MDM2 mRNA levels are not increased after DNA damage. This suggests that p53 is required for transcription of the MDM2 gene following DNA damage.