A systems view on DNA damage response kinetics in Tetrahymena

  1. Falk Butter1,2
  1. 1Institute of Molecular Biology (IMB), 55128 Mainz, Germany;
  2. 2Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, 17493 Greifswald, Germany;
  3. 3School of Health Sciences-Biomedical Sciences Program, Missouri State University, Springfield, Missouri 65897, USA

  1. ↵4 These authors contributed equally to this work.

  • ↵Present addresses: 5Department of Diagnostic and Interventional Radiology, Heidelberg University Hospital, 69120 Heidelberg, Germany; 6Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; 7Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; 8Division Systems Biology of Signal Transduction, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany

  • Corresponding author: falk.butter{at}fli.de

    • 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 six conditions (HU, MMS, IR, HP, cisplatin, and UV) and seven time points (from 0 to 8 h) 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.

    Footnotes

    • Received June 2, 2025.
    • Accepted January 21, 2026.

    This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see https://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.

    This Article

    1. Published in Advance January 28, 2026, doi: 10.1101/gr.281000.125 Genome Res. © 2026 Nischwitz et al.; Published by Cold Spring Harbor Laboratory Press

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    1. Profile for Butter, F.http://orcid.org/0000-0002-7197-7279

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