General features of the transcriptional response of mammalian cells to low- and high-LET irradiation

To understand the general features of the transcriptional response of mammalian cells to ionizing radiation we performed a meta-analysis of a transcriptomic dataset referring to 202 different irradiation conditions. Since there is a growing interest in the peculiarities of the response to high-LET versus low-LET irradiation, we enriched the dataset with high-LET conditions, Our results showed that the most general feature of the transcriptional response of mammalian cells to irradiation is the up-regulation CDKN1A which is universally observed in cancer and non-cancer cell lines and in highly proliferating tissues, such as skin, lymph node and blood. This induction does not require a wild-type P53 and is poorly radiation dose dependent. Moreover, it is observed at various times following both high- and low-LET irradiation. Among the genes mostly down-regulated by high-Let irradiation we found Pif1, a highly conserved protein that functions as DNA helicase and plays key roles in the protection of cells from DNA replication stress and DNA damage and in the maintenance of genome stability.