A systems view on DNA damage response kinetics in Tetrahymena
- Emily Nischwitz1,
- Vivien Schoonenberg2,
- Rachel Mullner3,
- Albert Fradera-Sola3,
- Susanne Zimbelmann4,
- Joshua J Smith5 and
- Falk Butter3,6
- 1 Institute of Molecular Biology (IMB), Heidelberg University Hospital;
- 2 Institute of Molecular Biology (IMB), Boston Children's Hospital, Harvard Medical School;
- 3 Institute of Molecular Biology (IMB), Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut;
- 4 Institute of Molecular Biology (IMB);
- 5 Missouri State University
Abstract
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 containing 6 conditions (HU, MMS, IR, HP, cisplatin, and UV) and 7 time points (from 0 to 8 hours) integrates over 250 paired transcriptome and proteome measurements. We observe 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 reveal 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. Ultimately, our study provides novel insights into the DNA damage response kinetics in Tetrahymena.
- Received June 2, 2025.
- Accepted January 21, 2026.
- Published by Cold Spring Harbor Laboratory Press
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