A systems view on DNA damage response kinetics

A tightly regulated DNA damage response is critical to the overall integrity of the genome. Here, we combine transcriptomics and proteomics to study DNA damage response kinetics across well-established treatments in the ciliate Tetrahymena thermophila. This extensive data set of 6 conditions (HU, MMS, IR, HP, cisplatin and UV) and 7 time points (from 0 to 8 hours) integrates over 250 transcriptome and proteome measurements. We observed upregulation of known DNA repair proteins as well as a global dynamic response of not yet characterized transcripts and proteins. Using artificial neural networks, we classify different expression trends in response to the damaging agents. These networks revealed both a core and specific global dynamic response to the different genotoxic stressors, highlighting unexpected pathway crosstalk. In addition to the comprehensive analysis presented here, the data can be explored via an accessible user interface at https://butterlab.imb-mainz.de/TtDDR/. Ultimately, our study provides novel insights into the DNA damage response kinetics in Tetrahymena.