Gentile Massimiliano, Latonen Leena, Laiho Marikki
Haartman Institute, University of Helsinki and Helsinki University Central Hospital, FIN-00014 Helsinki, Finland.
Nucleic Acids Res. 2003 Aug 15;31(16):4779-90. doi: 10.1093/nar/gkg675.
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.
紫外线辐射引起的DNA损伤会启动细胞恢复机制，这涉及DNA损伤反应途径的激活、细胞周期停滞和细胞凋亡。为了评估细胞对紫外线C（UVC）诱导的DNA损伤的转录反应，我们比较了人类皮肤成纤维细胞对已知分别诱导短暂细胞复制停滞或细胞凋亡的低剂量和高剂量UVC辐射的时间进程反应。UVC辐射在12000个转录本中的460个中引起了超过3倍的变化，其中89%代表下调的转录本。在低剂量和高剂量辐射中，只有5%的受调控基因是相同的。受到低剂量UVC照射的细胞表现出转录谱，显示出短暂调控后恢复，而高剂量照射后的反应则持续存在。对这些靶点进行的详细聚类分析和功能分类暗示了对生物学上不同反应的调控，并表明转录和翻译机制、炎症、抗增殖和抗血管生成反应均参与其中。这些数据支持了UVC辐射诱导显著的、剂量依赖性转录下调的观点。然而，数据强烈表明转录抑制也是靶基因选择性的。此外，结果表明UVC辐射诱导的细胞周期停滞和细胞凋亡的剂量依赖性在转录上是高度不同的反应。
