Repair of psoralen-treated DNA by genetic recombination in human cells infected with herpes simplex virus.
Herpes simplex virus type 1 was treated with 4,5'-8-trimethylpsoralen (psoralen) plus near-ultraviolet light in order to produce lesions (monoadducts and DNA cross-links) in the viral DNA. Human fibroblasts were infected by damaged virus under conditions in which either a single virus particle or several particles entered a given cell, and the fraction of virus-producing cells was determined. This fraction was significantly greater for multiply infected cells than for singly infected cells, indicating that the psoralen lesions are repaired more efficiently in the present of homologous, damaged DNA (multiplicity reactivation). Evidence is presented that herpes simplex virus may code for functions which participate in its own repair, both during multiplicity reactivation and during repair which occurs in singly infected cells: (a) host cells deficient in repair of lesions induced by psoralen (xeroderma pigmentosum) or the DNA cross-linking agent mitomycin C (Fanconi's anemia) exhibited normal levels of multiplicity reactivation of psoralen-treated herpes virus; (b) while xeroderma pigmentosum cells have been previously shown to be deficient in repair of psoralen-treated adenovirus under conditions of single infection, herpes virus is repaired at near normal levels in these same cells. Recombination levels between genetically marked pairs of herpes viruses were found to increase after treatment of the parental viruses with psoralen, suggesting that psoralen damage stimulates genetic recombination. This stimulation provides convincing evidence for a repair pathway in which genetic recombination between damaged viral genomes can lead to the production of viable virus.
D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D004260:DNA Repair; D004279:DNA, Viral / Q000235:genetics; D011564:Furocoumarins / Q000494:pharmacology*; D006801:Humans; D011995:Recombination, Genetic / Q000187:drug effects*; D018139:Simplexvirus / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects
D004279:DNA, Viral; D011564:Furocoumarins