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. Overall design: RNA-seq analysis of yeast containing either a Dsup expressing plasmid or empty vector after treatment with 0mM, 4mM or 8mM H2O2.