Cyclobutane pyrimidine dimers in UV-DNA induce release of soluble mediators that activate the human immunodeficiency virus promoter.
Ultraviolet (UV) irradiation of human cells induced expression of a stably maintained fusion gene consisting of the human immunodeficiency virus long terminal repeat promoter controlling the bacterial chloramphenicol acetyltransferase gene. Two experiments demonstrated that DNA damage can initiate induction: UV induction was greater in DNA repair-deficient cells from a xeroderma pigmentosum patient than in repair-proficient cells, and transfection of UV-irradiated DNA into unirradiated cells activated gene expression. Increased repair of cyclobutane pyrimidine dimers by T4 endonuclease V abrogated viral gene activation, suggesting that dimers in DNA are one signal leading to increased gene expression. This signal was spread from UV-irradiated cells to unirradiated cells by co-cultivation, implicating the release of soluble factors. Irradiation of cells from DNA repair-deficiency diseases resulted in greater release of soluble factors than irradiation of cells from unaffected individuals. These results suggest that UV-induced cyclobutane pyrimidine dimers can activate the human immunodeficiency virus promoter at least in part by a signal-transduction pathway that includes secretion of soluble mediators.
Applied Genetics Inc., Freeport, New York.
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Yarosh
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Alas
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Kibitel
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O'Connor
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Carrier
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Fornace
D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis*; D004247:DNA / Q000528:radiation effects*; D004790:Enzyme Induction / Q000528:radiation effects; D015967:Gene Expression Regulation, Viral / Q000528:radiation effects*; D005814:Genes, Viral / Q000235:genetics; D006678:HIV / Q000235:genetics* / Q000528:radiation effects*; D006801:Humans; D011401:Promoter Regions, Genetic; D011740:Pyrimidine Dimers / Q000494:pharmacology*; D013539:Simian virus 40 / Q000502:physiology; D015533:Transcriptional Activation; D014466:Ultraviolet Rays; D014764:Viral Proteins / Q000096:biosynthesis
D011740:Pyrimidine Dimers; D014764:Viral Proteins; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase