Induction of murine O6-alkylguanine-DNA-alkyltransferase in response to ionising radiation is p53 gene dose dependent.
Expression of both the DNA repair protein O6-alkylguanine-DNA-alkyltransferase (ATase) and the p53 tumour suppressor protein are inducible by a number of DNA damaging agents. It is probable that DNA strand breaks are the common inducing signals. This similarity, and the function of p53 as a transcription factor lead us to reason that p53 might be involved in ATase inducibility. We now report that the induction of ATase activity in mouse tissues following gamma-radiation is p53 gene dose dependent. While the extent and kinetics of induction in p53 wildtype mice are consistent with previous reports (a 2-3-fold peak increase at 36 h), no induction is observed in p53 null animals. Importantly the heterozygous mice show an intermediate response but the same kinetics. The basal levels of expression in all tissues examined are unaffected by p53 status. These data represent the first report of a discrete DNA repair function being p53 regulated in vivo and their potential clinical implications are discussed.
Rafferty
J A
JA
Cancer Research Campaign Department of Carcinogenesis, Paterson Institute for Cancer Research, Christie Hospital (NHS Trust), Manchester.
Clarke
A R
AR
Sellappan
D
D
Koref
M S
MS
Frayling
I M
IM
Margison
G P
GP
D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000201:enzymology; D002453:Cell Cycle; D004790:Enzyme Induction / Q000528:radiation effects; D005720:Gamma Rays; D018628:Gene Dosage; D016158:Genes, p53; D006579:Heterozygote; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008297:Male; D008780:Methyltransferases / Q000096:biosynthesis* / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008954:Models, Biological; D019853:O(6)-Methylguanine-DNA Methyltransferase; D013045:Species Specificity; D014157:Transcription Factors / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D014916:Whole-Body Irradiation
D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase