Involvement of DNA replication in ultraviolet-induced apoptosis of mammalian cells.
Exposure of cells to ultraviolet (UV) light damages the genome and the persistence of DNA lesions triggers apoptosis in mammalian cells. RNA transcription blockage by DNA damage is believed to be implicated in signaling for UV-induced apoptosis, but the role played by DNA replication in this process is still unclear. To address this point, we have employed the DNA polymerase inhibitor aphidicolin in UV-irradiated wild-type and XPB-mutated Chinese hamster ovary cells. The data obtained with synchronized cells indicate that induction of apoptosis by UV light is independent of the cell cycle phase. Nevertheless, cells treated with aphidicolin after UV exposure showed a significant prevention of apoptosis induction when compared to proliferating cells. These results were observed in both DNA-repair proficient and deficient cells, indicating that the prevention of apoptosis by aphidicolin is independent of the cells' ability to repair the photolesions caused by UV. Taken together, these data suggest that replication of damaged DNA also leads to critical events signaling for UV-induced cell death.
Batista
Luis Francisco Zirnberger
LF
Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, 05508-900 SP, Brazil.
Chiganças
Vanessa
V
Brumatti
Gabriela
G
Amarante-Mendes
Gustavo Pessini
GP
Menck
Carlos Frederico Martins
CF
D000818:Animals; D016590:Aphidicolin / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D016466:CHO Cells; D002453:Cell Cycle / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006224:Cricetinae; D003412:Cricetulus; D004261:DNA Replication / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D004307:Dose-Response Relationship, Radiation; D005434:Flow Cytometry; D008856:Microscopy, Fluorescence; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014466:Ultraviolet Rays
D016590:Aphidicolin