Multivalent binding of the tardigrade Dsup protein to chromatin promotes yeast survival and longevity upon exposure to oxidative damage
Tardigrades are remarkable in their ability to survive extreme environments. The damage suppressor (Dsup) protein is thought to contribute to their extreme resistance to reactive oxygen species (ROS) generated by irradiation. Here we show that expression of Ramazzottius varieornatus Dsup in Saccharomyces cerevisiae reduces oxidative DNA damage and extends lifespan in response to chronic oxidative genotoxicity. Dsup uses multiple modes of engagement with the nucleosomal H2A/H2B acidic patch, H3/H4 histone tails and DNA to bind across the yeast genome without bias. Effective chromatin binding and genome protection requires the Dsup HMGN-like motif and C-terminal sequences. These findings give precedent and mechanistic understanding for engineering an organism by physically shielding its genome to promote survival and longevity in the face of oxidative damage.
Authors
- Abraham Shim (ORCID: https://orcid.org/0000-0001-5351-0774)
- Brian D. Strahl (ORCID: https://orcid.org/0000-0002-4947-6259)
- Michael‐Christopher Keogh (ORCID: https://orcid.org/0000-0002-2219-8623)
- Matthew R. Marunde (ORCID: https://orcid.org/0009-0007-5934-7200)
- Kaylah Birmingham
- Nina Arslanovic (ORCID: https://orcid.org/0000-0001-5527-0874)
- Thea Grauer
- Jessica K. Tyler (ORCID: https://orcid.org/0000-0001-9765-1659)
- Ujani Chakraborty (ORCID: https://orcid.org/0000-0002-9308-3954)
- Richard Garner (ORCID: https://orcid.org/0000-0003-4475-8721)
- Laylo Mukhsinova (ORCID: https://orcid.org/0009-0008-7689-3497)
- Martis W. Cowles (ORCID: https://orcid.org/0000-0002-0469-0657)
- Allison R. Hickman (ORCID: https://orcid.org/0009-0007-7901-6687)
- Sabrina R. Hunt (ORCID: https://orcid.org/0000-0003-1873-3846)
- Rachel Watson (ORCID: https://orcid.org/0000-0002-5162-7503)
- Rhiannon R. Aguilar (ORCID: https://orcid.org/0000-0001-5723-608X)
- Christopher K. Cummins
- Bryan J. Venters (ORCID: https://orcid.org/0000-0002-4607-0587)
- Ryan J. Ezell
- J Ignacio Gutierrez (ORCID: https://orcid.org/0000-0002-9017-8384)
- Hannah Willis (ORCID: https://orcid.org/0009-0001-5996-2322)
- Laiba F Khan (ORCID: https://orcid.org/0009-0000-5427-0653)
- Kritika Kasliwal (ORCID: https://orcid.org/0000-0003-0004-1593)
- Spike D. L. Posnikoff
Institutions
- University of North Carolina at Chapel Hill (US)
- Cornell University (US)
- Tri-Institutional PhD Program in Chemical Biology (US)
- EpiCypher (United States) (US)
- Weill Cornell Medicine (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-09-29
- DOI
- https://doi.org/10.1038/s41467-025-63652-3
- Citations
- 6
- Primary Topic
- Tardigrade Biology and Ecology
- Type
- article
- Field-Weighted Citation Impact
- 18.16
Funders
- National Institutes of Health
- Weill Cornell Medical College
- National Institute of General Medical Sciences