Direct testing identifies conserved orthologous relationships with MutSβ in fission and budding yeast. Negative interactions from fission yeast were tested for orthologous conservation and potential synthetic chemo-sensitivity in budding yeast. msh2Δ- or msh3Δ-containing strains were created by plasmid shuffling and spotted as serial 10-fold dilutions onto the indicated medium (see Methods). To facilitate cross-comparison results are expressed by a color-code indicating the growth of each strain on a six-point scale relative to wild-type in each condition (all after incubation at 30C for 72h). rad55Δ is a positive control for genotoxin sensitivity . Hatch-bar, not tested; YPD, non-selective media; CPT (5μM); MMS (0.005%); HU (5mM); 5-FU (L ow dose, 38μM); 5-FU (H igh dose, 76μM).