Ultraviolet radiation-induced DNA damage in promoter elements inhibits gene expression.
Repair of DNA damage in gene promoters is slower than in actively transcribed genes. Persistent damage in gene promoters though transient can have significant biological effects on regulated gene expression. In this study we investigated the effect of ultraviolet radiation on gene promoter-associated functions when DNA damage is located within and outside transcription factor binding sites. Our results show that both cyclobutane pyrimidine dimers and (6-4) photoproducts inhibit DNA-protein interaction, in vitro transcript production and transactivation of reporter genes. The biological significance of transient DNA damage as a mechanism in carcinogenesis is discussed.
Ghosh
Rita
R
Department of Cancer Causation and Prevention, AMC Cancer Research Centre and the University of Colorado Comprehensive Cancer Centre, 1600 Pierce Street, Denver, CO 80214, USA. ghoshr@amc.org
Tummala
Ramakumar
R
Mitchell
David L
DL
D000818:Animals; D002460:Cell Line; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects*; D004249:DNA Damage; D004255:Deoxyribodipyrimidine Photo-Lyase / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D004330:Drosophila; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation / Q000528:radiation effects*; D017930:Genes, Reporter / Q000502:physiology / Q000528:radiation effects; D008156:Luciferases / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000528:radiation effects; D011401:Promoter Regions, Genetic / Q000528:radiation effects*; D011740:Pyrimidine Dimers / Q000737:chemistry / Q000528:radiation effects; D011863:Radioimmunoassay; D014158:Transcription, Genetic / Q000528:radiation effects; D014466:Ultraviolet Rays
D016328:NF-kappa B; D011740:Pyrimidine Dimers; D004247:DNA; D008156:Luciferases; D004255:Deoxyribodipyrimidine Photo-Lyase