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 st ably maintained fusion gene consisting of the human immunodeficiency v irus long terminal repeat promoter controlling the bacterial chloramph enicol acetyltransferase gene. Two experiments demonstrated that DNA d amage can initiate induction: UV induction was greater in DNA repair-d eficient cells from a xeroderma pigmentosum patient than in repair-pro ficient cells, and transfection of UV-irradiated DNA into unirradiated cells activated gene expression. increased repair of cyclobutane pyri midine dimers by T4 endonuclease V abrogated viral gene activation, su ggesting that dimers in DNA are one signal leading to increased gene e xpression. This signal was spread from UV-irradiated cells to unirradi ated cells by co-cultivation, implicating the release of soluble facto rs. Irradiation of cells from DNA repair-deficiency diseases resulted in greater release of soluble factors than irradiation of cells from u naffected individuals. These results suggest that UV-induced cyclobuta ne pyrimidine dimers can activate the human immunodeficiency virus pro moter at least in part by a signal-transduction pathway that includes secretion of soluble mediators.