Multivalent binding of the tardigrade Dsup protein to heterologous 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 responsible for 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 the lifespan of budding yeast with chronic oxidative damage. This protection from ROS requires either the Dsup HMGN-like domain or sequences C-terminal to same. Dsup associates with no apparent bias across the yeast genome, using multiple modes of nucleosome binding; the HMGN-like region interacts with both the H2A/H2B acidic patch and H3/H4 histone tails, while the C-terminal region binds DNA. These findings give precedent for engineering an organism by physically shielding its genome to promote survival and longevity in the face of oxidative damage. Overall design: 12 CUT&RUN samples including three targets (IgG, H3K4me3, and FLAG) across yeast cells with four various Ramazzottius varieornatus Dsup plasmid integrations. Control target=IgG, Control condition=Empty Vector.