Meiotic chromosomes have a loop/axis architecture, with axis length determining crossover frequency. Meiosis-specific Pds5 depletion mutants have shorter chromosome axes and lower homologous chromosome pairing and recombination frequency. However, it is poorly understood how Pds5 coordinately regulates these processes. In this study, we show that only ~20% of wild-type level of Pds5 is required for homolog pairing and that higher levels of Pds5 dosage-dependently regulate axis length and crossover frequency. Moderate changes in Pds5 protein levels do not explicitly impair the basic recombination process. Further investigations show that Pds5 does not regulate chromosome axes by altering Rec8 abundance. Conversely, Rec8 regulates chromosome axis length by modulating Pds5. These findings highlight the important role of Pds5 in regulating meiosis and its relationship with Rec8 to regulate chromosome axis length and crossover frequency with implications for evolutionary adaptation.
Metabolic engineering of Saccharomyces cerevisiae for high‐level production of aromatic chemicals has received increasing attention in recent years. Tyrosol production from glucose by S. cerevisiae is considered an environmentally sustainable and safe approach. However, the production of tyrosol and salidroside by engineered S. cerevisiae has been reported to be lower than 2 g/L to date. In this study, S. cerevisiae was engineered with a push‐pull‐restrain strategy to efficiently produce tyrosol and salidroside from glucose. The biosynthetic pathways of ethanol, phenylalanine, and tryptophan were restrained by disrupting PDC1, PHA2, and TRP3. Subsequently, tyrosol biosynthesis was enhanced with a metabolic pull strategy of introducing PcAAS and EcTyrAM53I/A354V. Moreover, a metabolic push strategy was implemented with the heterologous expression of phosphoketolase (Xfpk), and then erythrose 4‐phosphate was synthesized simultaneously by two pathways, the Xfpk‐based pathway and the pentose phosphate pathway, in S. cerevisiae. Furthermore, the heterologous expression of Xfpk alone in S. cerevisiae efficiently improved tyrosol production compared with the coexpression of Xfpk and phosphotransacetylase. Finally, the tyrosol yield increased by approximately 135‐folds, compared with that of parent strain. The total amount of tyrosol and salidroside with glucose fed‐batch fermentation was over 10 g/L and reached levels suitable for large‐scale production.
Meiotic recombination is integrated into and regulated by meiotic chromosomes, which is organized as loop/axis architecture. However, the regulation of chromosome organization is poorly understood. Here, we show Esa1, the NuA4 complex catalytic subunit, is constitutively expressed and localizes on chromatin loops during meiosis. Esa1 plays multiple roles including homolog synapsis, sporulation efficiency, spore viability, and chromosome segregation in meiosis. Detailed analyses show the meiosis-specific depletion of Esa1 results in decreased chromosome axis length independent of another axis length regulator Pds5, which further leads to a decreased number of Mer2 foci, and consequently a decreased number of DNA double-strand breaks, recombination intermediates, and crossover frequency. However, Esa1 depletion does not impair the occurrence of the obligatory crossover required for faithful chromosome segregation, or the strength of crossover interference. Further investigations demonstrate Esa1 regulates chromosome axis length via acetylating the N-terminal tail of histone H4 but not altering transcription program. Therefore, we firstly show a non-chromosome axis component, Esa1, acetylates histone H4 on chromatin loops to regulate chromosome axis length and consequently recombination frequency but does not affect the basic meiotic recombination process. Additionally, Esa1 depletion downregulates middle induced meiotic genes, which probably causing defects in sporulation and chromosome segregation.
Highlights d RNA-DNA hybrids form at ssDNA ends of meiotic DNA double-strand break sites d Formation of meiotic RNA-DNA hybrids requires Rad52 d RNA-DNA hybrids regulate the homolog bias in meiotic recombination d RNA-DNA hybrids modulate both crossover and noncrossover recombination
Significance Meiotic crossover recombination is required for faithful chromosome segregation and promotes genetic diversity by reshuffling alleles between parental chromosomes. Meiotic chromosomes are organized into arrays of loops that are anchored to the proteinaceous axes. The length of the meiotic chromosome axis is intimately associated with crossover frequencies in yeast and higher eukaryotes. However, how chromosome axis length is regulated in meiosis is unknown. Here, we demonstrate that cohesin regulator Pds5 interacts with proteasomes to regulate meiotic chromosome axis length by modulating ubiquitination. This regulatory mechanism also includes two ubiquitin E3 ligases, SCF (Skp–Cullin–F-box) and Ufd4. These findings identify a molecular pathway in regulating chromosome organization and reveal an unexpected function of the ubiquitin–proteasome system in meiosis.
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