Defining the spectrum of cellular protection against cadmium stress by Dsup expressed in yeast

The intrinsically disordered tardigrade Dsup protein has garnered attention for its ability to protect cells and organisms from radiation and oxidative stress. Our lab has previously described Dsups protective effect in yeast, finding that, while Dsup expression comes with a fitness cost, it improves survival under many stressors, including the heavy metal cadmium. While Dsups protection against oxidative stress and radiation is well-established, the mechanism by which it protects against other stressors is underinvestigated. To address this knowledge gap, we screened a collection of 4000 yeast deletion mutants expressing Dsup in the presence of three doses of cadmium to identify synergistic/synthetically lethal genes and processes. We find that Dsup broadly buffers many processes/genes at lower levels of cadmium stress but at higher doses, cells shift to buffering specific genes/processes. These results identify host genetic processes that influence Dsups ability to confer cadmium resistance to organisms.