Mark Johnston

Regulators of the well-studied GAL genes of the yeast Saccharomyces cerevisiae continue to be identified! The authors identified TORC1 components tor1 and tco89, and the downstream PP2A/Cdc55 phosphatase as regulators of Gal4 in S. cerevisiae. Additionally, genetic analysis indicated that mutations in hom3 encoding aspartate kinase produce defects in TOR signalling. The results demonstrate that regulation of Gal4 by phosphorylation is modulated by the TOR nutritional signalling pathway through the activity of PP2A/Cdc55.

Changes in a pheromone/receptor system can alter species-specificity during the selection of a mating partner. This study examined differences in the stringency of two receptors (Map3 and Mam2) in recognizing pheromones in the fission yeast Schizosaccharomyces pombe. The findings indicate that Map3 may play a role in prevention of interspecies mating, and that the 6th transmembrane region is likely to be important for its activation by M-factor.

The term interchromosomal effect was originally used to describe a change in the distribution of exchange in the presence of an inversion. First characterized in the 1920s by early Drosophila researchers, it has been observed in multiple organisms. Nearly half a century later, the term began to appear in the human genetics literature to describe the hypothesis that parental chromosome differences, such as translocations or inversions, may increase the frequency of meiotic chromosome nondisjunction. Although it remains unclear if chromosome aberrations truly affect the segregation of structurally normal chromosomes in humans, the use of the term interchromosomal effect in this context persists. This article explores the history of the use of the term interchromosomal effect and discusses how chromosomes with structural aberrations are segregated during meiosis.

These investigators evolved the naturally competent Bacillus subtilis in the presence or absence of foreign genomic DNA. They examined the effects of foreign DNA acquisition on the growth improvement of the evolving bacteria and on their genomes. They show that extensive acquisition of DNA from close strains occurs, often in bursts, and introduces multitudes of single nucleotide variations that propagate in the population under selection. They show a connection between the integration of the foreign DNA and fitness improvement, highlighting the role of horizontal gene transfer in bacterial adaptation.

Aspergillus fumigatus is a major fungal pathogen of humans but its two closest relatives, Aspergillus fischeri and Aspergillus oerlinghausenensis, are not. These investigators examined whether A. fumigatus secondary metabolites, some of which are known genetic determinants of A. fumigatus virulence, and the metabolic pathways that produce them, are conserved in A. oerlinghausenensis and A. fischeri. They found that the nonpathogenic relatives of A. fumigatus produce some, but not all, secondary metabolites thought to contribute to the success of A. fumigatus in causing human disease and that these similarities and differences are reflected in the underlying metabolic pathways involved in their biosynthesis.

Meiosis in the budding yeast Saccharomyces cerevisiae is used to create haploid yeast spores from a diploid mother cell. During meiosis II, cytokinesis occurs by closure of the prospore membrane, a membrane that initiates at the spindle pole body and grows to surround each of the haploid meiotic products. Timely prospore membrane closure requires SPS1, which encodes an STE20 family GCKIII kinase. To identify genes that may activate SPS1, we utilized a histone phosphorylation defect of sps1 mutants to screen for genes with a similar phenotype and found that cdc15 shared this phenotype. CDC15 encodes a Hippo-like kinase that is part of the mitotic exit network. We find that Sps1 complexes with Cdc15, that Sps1 phosphorylation requires Cdc15, and that CDC15 is also required for timely prospore membrane closure. We also find that SPS1, like CDC15, is required for meiosis II spindle disassembly and sustained anaphase II release of Cdc14 in meiosis. However, the NDR-kinase complex encoded by DBF2/DBF20MOB1 which functions downstream of CDC15 in mitotic cells, does not appear to play a role in spindle disassembly, timely prospore membrane closure, or sustained anaphase II Cdc14 release. Taken together, our results suggest that the mitotic exit network is rewired for exit from meiosis II, such that SPS1 replaces the NDR-kinase complex downstream of CDC15. Copyright © 2020 by the Genetics Society of America.

Breaks in the strands of DNA threaten the genetic integrity of all organisms, which have many mechanisms to repair this type of DNA damage. RecA and RecN are examples of DNA repair proteins that participate in double-strand-break repair. Their role in this mechanism is not well understood. Others have hypothesized that these two proteins interact to repair DNA and that a particular amino acid in RecA is critical for this interaction. These authors tested this model through genetic epistasis analysis and found it is not supported.

The opportunistic human fungal pathogen Candida albicans switches between two distinct, heritable cell types named “white” and “opaque.” Lohse et al. show that opaque cells, in response to proteins as the sole nitrogen source, up-regulate a specialized program, including specific secreted aspartyl proteases and peptide transporters. They demonstrate that, in mixed cultures, opaque cells enable white cells to respond and proliferate more efficiently under these conditions. These observations suggest that white-opaque switching creates mixtures of cells where the population characteristics, which derive from a single genome, reflect the contributions of two distinct cell types.

Heat-shock protein (Hsp) 90 assists in the folding of diverse sets of client proteins including kinases and growth hormone receptors. Hsp70 plays a major role in many Hsp90 functions by interacting and modulating conformation of its substrates before being transferred to Hsp90s for final maturation. Each eukaryote contains multiple members of the Hsp70 family. However, the role of different Hsp70 isoforms in Hsp90 chaperoning actions remains unknown. Using v-Src as an Hsp90 substrate, we examined the role of each of the four yeast cytosolic Ssa Hsp70s in regulating Hsp90 functions. We show that the strain expressing stress-inducible Ssa3 or Ssa4, and the not constitutively expressed Ssa1 or Ssa2, as the sole Ssa Hsp70 isoform reduces v-Src-mediated growth defects. The study shows that although different Hsp70 isoforms interact similarly with Hsp90s, v-Src maturation is less efficient in strains expressing Ssa4 as the sole Hsp70. We further show that the functional distinction between Ssa2 and Ssa4 is regulated by its C-terminal domain. Further studies reveal that Ydj1, which is known to assist substrate transfer to Hsp70s, interacts relatively weakly with Ssa4 compared with Ssa2, which could be the basis for poor maturation of the Hsp90 client in cells expressing stress-inducible Ssa4 as the sole Ssa Hsp70. The study thus reveals a novel role of Ydj1 in determining the functional distinction among Hsp70 isoforms with respect to the Hsp90 chaperoning action. Copyright © 2020 by the Genetics Society of America.