During meiosis, programmed double strand breaks (DSBs) are repaired preferentially between homologs to generate crossovers that promote proper chromosome segregation at Meiosis I. In many organisms, there are two strand exchange proteins, Rad51 and the meiosis-specific Dmc1, required for interhomolog (IH) bias. This bias requires the presence, but not the strand exchange activity of Rad51, while Dmc1 is responsible for the bulk of meiotic recombination. How these activities are regulated is less well established. In dmc1Δ mutants, Rad51 is actively inhibited, thereby resulting in prophase arrest due to unrepaired DSBs triggering the meiotic recombination checkpoint. This inhibition is dependent upon the meiosis-specific kinase Mek1 and occurs through two different mechanisms that prevent complex formation with the Rad51 accessory factor Rad54: (i) phosphorylation of Rad54 by Mek1 and (ii) binding of Rad51 by the meiosis-specific protein Hed1. An open question has been why inhibition of Mek1 affects Hed1 repression of Rad51. This work shows that Hed1 is a direct substrate of Mek1. Phosphorylation of Hed1 at threonine 40 helps suppress Rad51 activity in dmc1Δ mutants by promoting Hed1 protein stability. Rad51-mediated recombination occurring in the absence of Hed1 phosphorylation results in a significant increase in non-exchange chromosomes despite wild-type levels of crossovers, confirming previous results indicating a defect in crossover assurance. We propose that Rad51 function in meiosis is regulated in part by the coordinated phosphorylation of Rad54 and Hed1 by Mek1.

Sporulation of budding yeast is a developmental process in which cells undergo meiosis to generate stress-resistant progeny. The dynamic nature of the budding yeast meiotic transcriptome has been well established by a number of genome-wide studies. Here we develop an analysis pipeline to systematically identify novel transcription start sites that reside internal to a gene. Application of this pipeline to data from a synchronized meiotic time course reveals over 40 genes that display specific internal initiations in mid-sporulation. Consistent with the time of induction, motif analysis on upstream sequences of these internal transcription start sites reveals a significant enrichment for the binding site of Ndt80, the transcriptional activator of middle sporulation genes. Further examination of one gene, MRK1, demonstrates the Ndt80 binding site is necessary for internal initiation and results in the expression of an N-terminally truncated protein isoform. When the MRK1 paralog RIM11 is downregulated, the MRK1 internal transcript promotes efficient sporulation, indicating functional significance of the internal initiation. Our findings suggest internal transcriptional initiation to be a dynamic, regulated process with potential functional impacts on development.

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The fungal pathogen Candida albicans has a complex relationship with human hosts. Under many conditions, it grows as a harmless commensal organism on the skin and GI tract mucosa (Kumamoto et al., 2020;Romo & Kumamoto, 2020). However, overgrowth of C. albicans due to conditions such as biofilm formation on medical devices or changes in the microbiome caused by antibacterial antibiotics can develop into lethal invasive infections in a wide range of different tissues (Kullberg & Arendrup, 2015;Noble et al., 2017;Pfaller & Castanheira, 2016). This is a special concern for immunocompromised patients who are more susceptible to infection (Brown et al., 2012). A key virulence factor for C. albicans is its ability to resist stress (Brown et al., 2014). The host immune system employs a wide range of defensive strategies including elevated temperature, oxidative and nitrosative stress, antimicrobial peptides, and regulation of micronutrients such as iron depletion or copper toxicity (Brown et al., 2009;Dantas

In the Data Availability statement, the link for accessing the processed recombination analysis files in Dryad is incorrect. The correct link is http://dx.doi.org/10.5061/dryad.g6s2k.