Journal article
Biochemical and Structural Analyses of the Tardigrade DNA-Damage Suppressor Protein, Dsup
Journal of molecular biology, Vol.437(24), 169490
12/15/2025
DOI: 10.1016/j.jmb.2025.169490
PMCID: PMC12875066
PMID: 41115570
Abstract
Tardigrades are extremophiles that withstand harsh environments through unique molecular strategies. One such strategy involves Damage Suppressor (Dsup), a protein shown to protect cells from radiation-induced DNA damage. Little is known about the biochemical and structural characteristics of Dsup that lead to DNA protection. To gain insight into the mechanism of DNA protection by Dsup, we examined its fundamental biochemical and structural properties using mass photometry, biolayer interferometry, small-angle X-ray scattering, and microfluidic modulation spectroscopy. We found that Dsup is largely intrinsically disordered and binds DNA with high affinity via a multi-valent interface. This interaction induced conformational changes in both Dsup and the DNA, suggesting a potential structural mechanism of its DNA protection ability. We propose that Dsup alters DNA structure, possibly by partially unwinding it, to reduce its susceptibility to damage. These findings offer new insights into how a disordered protein such as Dsup functions as radioprotectants in extreme environments.
Details
- Title: Subtitle
- Biochemical and Structural Analyses of the Tardigrade DNA-Damage Suppressor Protein, Dsup
- Creators
- Tyler J Woodward - University of IowaM Todd Washington - University of Iowa, Biochemistry and Molecular Biology
- Resource Type
- Journal article
- Publication Details
- Journal of molecular biology, Vol.437(24), 169490
- DOI
- 10.1016/j.jmb.2025.169490
- PMID
- 41115570
- PMCID
- PMC12875066
- NLM abbreviation
- J Mol Biol
- ISSN
- 0022-2836
- eISSN
- 1089-8638
- Publisher
- ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
- Grant note
- National Institute of General Medical Sciences: R35 GM148186
This work was supported by award R35 GM148186 to M.T.W. from the National Institute of General Medical Sciences. The content is solely the responsibility of the authors and does not necessarily reflect the official views of the National Institute of General Medical Sciences or the National Institutes of Health. We thank Maria Spies, Lynne Dieckman, Bret Freudenthal, Christine Kondratick, Zach Frevert, Sarah Jordan, and Luke Handlos for discussions. We thank James Kadonaga at University of California San Diego for the Dsup-expressing plasmid. We thank Wellington Leite at Oak Ridge National Laboratory (Oak Ridge, TN) for collecting small-angle X-ray data. We also thank Richard Huang at RedShiftBio (Boston, MA) for collecting and analyzing the microfluidic modulation spectroscopic data.
- Language
- English
- Electronic publication date
- 10/18/2025
- Date published
- 12/15/2025
- Academic Unit
- Radiation Oncology; Biochemistry and Molecular Biology
- Record Identifier
- 9985016824402771
Metrics
50 Record Views