title: Cell cycle arrest and apoptosis provoked by UV radiation-induced DNA damage are transcriptionally highly divergent responses.
abstract: DNA damage caused by UV radiation initiates cellular recovery mechanisms, which involve activation of DNA damage response pathways, cell cycle arrest and apoptosis. To assess cellular transcriptional responses to UVC-induced DNA damage we compared time course responses of human skin fibroblasts to low and high doses of UVC radiation known to induce a transient cellular replicative arrest or apoptosis, respectively. UVC radiation elicited >3-fold changes in 460 out of 12,000 transcripts and 89% of these represented downregulated transcripts. Only 5% of the regulated genes were common to both low and high doses of radiation. Cells inflicted with a low dose of UVC exhibited transcription profiles demonstrating transient regulation followed by recovery, whereas the responses were persistent after the high dose. A detailed clustering analysis and functional classification of the targets implied regulation of biologically divergent responses and suggested involvement of transcriptional and translational machinery, inflammatory, anti-proliferative and anti-angiogenic responses. The data support the notion that UVC radiation induces prominent, dose-dependent downregulation of transcription. However, the data strongly suggest that transcriptional repression is also target gene selective. Furthermore, the results demonstrate that dose-dependent induction of cell cycle arrest and apoptosis by UVC radiation are transcriptionally highly distinct responses.
authors.affiliation: Haartman Institute, University of Helsinki and Helsinki University Central Hospital, FIN-00014 Helsinki, Finland.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Gentile
authors.forename: Leena
authors.initials: L
authors.lastname: Latonen
authors.forename: Marikki
authors.initials: M
authors.lastname: Laiho
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects*; D015152:Blotting, Northern; D002453:Cell Cycle / Q000235:genetics / Q000528:radiation effects*; D002460:Cell Line; D016000:Cluster Analysis; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000528:radiation effects; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D014158:Transcription, Genetic / Q000235:genetics / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D012313:RNA