Increased polysumoylation is lethal in msh2Δ fission yeast. (A) Deletion of the Ulp2 SUMO-protease is synthetic lethal (SL) with msh2Δ. msh2Δ and ulp2Δ strains were mated, sporulated, tetrads dissected and genotypes determined ((ulp2Δ/msh2Δ) is boxed). (B) Schematic depicts the sumoylation pathway. Fission yeast contains one gene encoding SUMO (Smt3), two E3-ligases (Pli1 and Nse2), and two SUMO proteases (Ulp1 and Ulp2). (C) msh2Δ is SL with ulp2Δ but neutral with ulp1Δ. Strains were mated, sporulated, and tetrads dissected. The number of viable spores observed/expected for each genotype is indicated (see also Additional file 1: Figure S2A and B). (D, E) smt3Δ or nse2-SA (catalytic dead), but not pli1Δ, rescue the lethality of (msh2Δ/ulp2Δ). Strains were mated, sporulated, and the indicated number of tetrads dissected (see also Additional file 1: Figure S2C to E). Panel (E) depicts representative tetrads to demonstrate the growth of each mutant combination.