Chromosomal DNA double-strand breaks (DSBs) are potentially lethal DNA lesions that pose a significant threat to genome stability and therefore need to be repaired to preserve genome integrity. Eukaryotic cells possess two main mechanisms for repairing DSBs: non-homologous end-joining (NHEJ) and homologous recombination (HR). HR requires that the 5′ terminated strands at both DNA ends are nucleolytically degraded by a concerted action of nucleases in a process termed DNA-end resection. This degradation leads to the formation of 3′-ended single-stranded DNA (ssDNA) ends that are essential to use homologous DNA sequences for repair. The evolutionarily conserved Mre11-Rad50-Xrs2/NBS1 complex (MRX/MRN) has enzymatic and structural activities to initiate DSB resection and to maintain the DSB ends tethered to each other for their repair. Furthermore, it is required to recruit and activate the protein kinase Tel1/ATM, which plays a key role in DSB signaling. All these functions depend on ATP-regulated DNA binding and nucleolytic activities of the complex. Several structures have been obtained in recent years for Mre11 and Rad50 subunits from archaea, and a few from the bacterial and eukaryotic orthologs. Nevertheless, the mechanism of activation of this protein complex is yet to be fully elucidated. In this review, we focused on recent biophysical and structural insights on the MRX complex and their interplay.

Though fungi show peculiarities in the purposes and specific traits of calcium signaling pathways, the general scheme and the most important players are well conserved if compared to higher eukaryotes. This provides a powerful opportunity either to investigate shared features using yeast as a model or to exploit fungal specificities as potential targets for antifungal therapies. The sequenced genomes from yeast Saccharomyces cerevisiae, Schizosaccharomyces pombe and the filamentous fungus Neurospora crassa were already published more than ten years ago. More recently the genome sequences of filamentous fungi of Aspergillus genus, some of which threatening pathogens, and dimorphic fungi Ustilago maydis were published, giving the chance to identify several proteins involved in calcium signaling based on their homology to yeast or mammalian counterparts. Nonetheless, unidentified calcium transporters are still present in these organisms which await to be molecularly characterized. Despite the relative simplicity in yeast calcium machinery and the availability of sophisticated molecular tools, in the last years, a number of new actors have been identified, albeit not yet fully characterized. This review will try to describe the state of the art in calcium channels and calcium signaling knowledge in yeast, with particular attention to the relevance of this knowledge with respect to pathological fungi.