Manganese Stress Tolerance Depends on Yap1 and Stress-Activated MAP Kinases.

Understanding which intracellular signaling pathways are activated by manganese stress is crucial to decipher how metal overload compromise cellular integrity. Here, we unveil a role for oxidative and cell wall stress signaling in the response to manganese stress in yeast. We find that the oxidative stress transcription factor Yap1 protects cells against manganese toxicity. Conversely, extracellular manganese addition causes a rapid decay in Yap1 protein levels. In addition, manganese stress activates the MAPKs Hog1 and Slt2 (Mpk1) and leads to an up-regulation of the Slt2 downstream transcription factor target Rlm1. Importantly, Yap1 and Slt2 are both required to protect cells from oxidative stress in mutants impaired in manganese detoxification. Under such circumstances, Slt2 activation is enhanced upon Yap1 depletion suggesting an interplay between different stress signaling nodes to optimize cellular stress responses and manganese tolerance.

Late rDNA Condensation Ensures Timely Cdc14 Release and Coordination of Mitotic Exit Signaling with Nucleolar Segregation.

The nucleolus plays a pivotal role in multiple key cellular processes. An illustrative example is the regulation of mitotic exit in Saccharomyces cerevisiae through the nucleolar sequestration of the Cdc14 phosphatase. The peculiar structure of the nucleolus, however, has also its drawbacks. The repetitive nature of the rDNA gives rise to cohesion-independent linkages whose resolution in budding yeast requires the Cdc14-dependent inhibition of rRNA transcription, which facilitates condensin accessibility to this locus. Thus, the rDNA condenses and segregates later than most other yeast genomic regions. Here, we show that defective function of a small nucleolar ribonucleoprotein particle (snoRNP) assembly factor facilitates condensin accessibility to the rDNA and induces nucleolar hyper-condensation. Interestingly, this increased compaction of the nucleolus interferes with the proper release of Cdc14 from this organelle. This observation provides an explanation for the delayed rDNA condensation in budding yeast, which is necessary to efficiently coordinate timely Cdc14 release and mitotic exit with nucleolar compaction and segregation.