Dual functions of Mdt1 in genome maintenance and cell integrity pathways in Saccharomyces cerevisiae.

Recent evidence indicates considerable cross-talk between genome maintenance and cell integrity control pathways. The RNA recognition motif (RRM)- and SQ/TQ cluster domain (SCD)-containing protein Mdt1 is required for repair of 3'-blocked DNA double-strand breaks (DSBs) and efficient recombinational maintenance of telomeres in budding yeast. Here we show that deletion of MDT1 (PIN4/YBL051C) leads to severe synthetic sickness in the absence of the genes for the central cell integrity MAP kinases Bck1 and Slt2/Mpk1. Consistent with a cell integrity function, mdt1Delta cells are hypersensitive to the cell wall toxin calcofluor white and the Bck1-Slt2 pathway activator caffeine. An RRM-deficient mdt1-RRM0 allele shares the severe bleomycin hypersensitivity, inefficient recombinational telomere maintenance and slt2 synthetic sickness phenotypes, but not the cell wall toxin hypersensitivity with mdt1Delta. However, the mdt1-RRM(3A) allele, where only the RNA-binding site is mutated, behaves similarly to the wild-type, suggesting that the Mdt1 RRM functions as a protein-protein interaction rather than a nucleic acid-binding module. Surprisingly, in a strain background where double mutants are sick but still viable, bck1Deltamdt1Delta and slt2Deltamdt1Delta mutants differ in some of their phenotypes, consistent with the emerging concept of flexible signal entry and exit points in the Bck1-Mkk1/2-Slt2 pathway. Overall, the results indicate that Mdt1 has partially separable functions in both cell wall and genome integrity pathways.