Biology subjects

Covo, S.

Publications and source records attributed to Covo, S..

7 recordsLinked to original sources

bioRxiv2026

UV-induced translation capacity is regulated developmentally in fungi.

In fast-growing cells, most RNA molecules encode ribosomal subunits. During growth arrest caused by DNA damage, ribosome biogenesis is reduced because it is a highly energy-demanding process. Here, we report that, in two filamentous fungi, UV radiation significantly induces ribosome levels and translation capacity. This UV-induced response is developmentally regulated and occurs after filament formation. Translation induction modestly but significantly enhances both UV survival and repair. While some of the mRNAs that are differentially associated with ribosomes following UV exposure are associated with DNA repair, most of them belong to modules involved in protein folding and gene expression. TOR signaling is required for the immediate UV induction of ribosome biogenesis genes. However, we provide evidence that UV induces mechanisms that operate either upstream of or in parallel with TOR. These findings suggest a novel type of response to DNA damage, in which the primary aim is to protect the integrity of gene expression from the detrimental effects of UV radiation on transcription.

microbiology↗

bioRxiv2026

The Ancient Origin and Dynamic Diversification of the Fungal Poly(ADP)-ribose Polymerase Protein Family

Poly(ADP-ribose) polymerases (PARPs) catalyze ADP-ribosylation, a conserved post- translational modification involved in DNA repair, transcriptional regulation, and chromatin remodeling. Although extensively studied in animals, the evolution and diversification of PARPs across the fungal kingdom remain largely unexplored. Here, we present the first kingdom-wide comparative genomic analysis of PARP proteins across 534 fungal species spanning eight phyla. We identified two primary conserved fungal PARP protein types corresponding to human PARP1 and PARP6. Both exhibit highly dynamic evolutionary histories characterized by frequent independent gain and loss events. Ancestral state reconstruction supports the presence of PARP1 in the last common ancestor of fungi, whereas the PARP6-like family has undergone repeated lineage-specific gains and losses. Fungal PARP6-like proteins retain a compact PARP catalytic domain fused to a C-terminal E2 ubiquitin-conjugating domain, whereas the PARP1 family displays extensive structural diversification through domain shuffling and lineage-specific fusions associated with DNA metabolism, chromatin remodeling, and signal transduction. Reconstruction of ancestral catalytic motifs across fungi and other eukaryotes revealed convergent evolution of a non-canonical H-Y-Y catalytic triad, with multiple motif variants co-occurring within individual proteins, suggesting functional diversification. In the Fusarium oxysporum species complex, we identified a lineage-specific expansion of the PARP family, driven exclusively by accessory chromosomes. Genomes with expanded PARP1 repertoires exhibited elevated basal PARylation, increased resistance to DNA-damaging agents that induce single strand breaks, and DNA damage- induced expression of accessory Parp genes. These findings reveal fungal PARPs as evolutionarily dynamic proteins that likely contribute to genome stability, adaptation, and pathogenicity.

evolutionary biology↗

bioRxiv2025

Stable hypermutators revealed by the genomic landscape of DNA repair genes among yeast species

Mutator phenotypes are short-lived due to the rapid accumulation of deleterious mutations. Yet, recent observations reveal that certain fungi can undergo prolonged accelerated evolution after losing DNA repair genes. Here, we surveyed 1,154 yeast genomes representing nearly all known yeast species of the subphylum Saccharomycotina to examine the relationship between reduced DNA repair repertoires and elevated evolutionary rates. We identified three distantly related lineages--encompassing 12% of species--with substantially reduced sets of DNA repair genes and the highest evolutionary rates in the entire subphylum. Two of these "faster-evolving lineages" (FELs)--a subclade within the order Pichiales and the Wickerhamiella/Starmerella (W/S) clade (order Dipodascales)--are described here for the first time, while the third corresponds to a previously documented Hanseniaspora FEL. Examination of DNA repair gene repertoires revealed a set of genes predominantly absent in these three FELs, suggesting a potential role in the observed acceleration of evolutionary rates. Genomic signatures in the W/S clade are consistent with a substantial mutational burden, including pronounced A|T bias and signatures of endogenous DNA damage. The W/S clade appears to mitigate UV-induced damage through horizontal acquisition of a bacterial photolyase gene, underscoring how gene loss may be offset by nonvertical evolution. These findings highlight how the loss of DNA repair genes gave rise to hypermutators that persist across macroevolutionary timescales, with horizontal gene transfer as an avenue for partial functional compensation.

evolutionary biology↗

bioRxiv2024

Whole-Plant Physiological Identification and Quantification of Disease Progression

Visual estimates of plant symptoms are traditionally used to quantify disease severity. Yet, the methodologies used to assess these phenotypes are often subjective and do not allow tracking of disease progression from very early stages. Here, we hypothesized that quantitative analysis of whole-plant physiological vital functions can be used to objectively determine plant health, providing a more sensitive way to detect disease. We studied the tomato wilt that is caused by Fusarium oxysporum f. sp. lycopersici. Physiological performance of infected and non-infected tomato plants was compared using a whole-plant pot-based lysimeter functional-phenotyping system in a semi-environmentally controlled greenhouse. Water-balance traits of the plants were measured continuously and simultaneously in a quantitative manner. Infected plants exhibited early reductions in transpiration and biomass gain, which preceded visual disease symptoms. These changes in transpiration proved to be effective quantitative indicators for assessing both plant susceptibility to infection and virulence of the fungus. Physiological changes linked to fungal outgrowth and toxin release contributed to reduced hydraulic conductance during initial infection stages. The functional-phenotyping method objectively captures early-stage disease progression, advancing plant disease research and management. This approach emphasizes the potential of quantitative whole-plant physiological analysis over traditional visual estimates for understanding and detecting plant diseases.

plant biology↗

bioRxiv2022

Checks and balances of the RTG pathway under arginine deprivation and canavanine exposure in Saccharomyces cerevisiae

Decades of research in Saccharomyces cerevisiae underlie the current dogma of mitochondrial retrograde (RTG) signaling: Rtg2-dependent translocation of the heterodimer Rtg1/Rtg3 from the cytoplasm to the nucleus induces the transcription of RTG-target genes under glutamate starvation or loss of respiration. We previously found that RTG mutants show severe growth inhibition from arginine deprivation and are highly sensitive to canavanine when grown on glucose. Here, we show that on solid media, RTG mutants are also sensitive to thialysine, a toxic lysine analog, although lysine deprivation causes a milder growth defect. Growth on an alternative carbon source restores RTG mutants ability to grow without arginine or lysine and improves their tolerance of toxic analogs; deletion of MIG1 affords a similar rescue on glucose and improves canavanine tolerance, except for in rtg2{Delta}. It is well known that the target of rapamycin (TOR) signaling pathway inhibits the RTG pathway. Batch growth experiments with or without TOR inhibition reveal phenotypic and regulatory differences between RTG mutants. rtg1{Delta} can sustain simultaneous canavanine exposure and TOR inhibition via rapamycin, but rtg2{Delta} and rtg3{Delta} cannot. Surprisingly, our data show that under fermentative lifestyle and arginine deprivation, both RTG signaling and TOR activity are required. This expands the universe of TOR and RTG signaling, suggesting bilateral communication rather than unidirectional RTG regulation by TOR. To the best of our knowledge, this work shows for the first time that Rtg3 activity can be separate from its role as a heterodimer with Rtg1. This work also strongly suggests a specific role for Rtg2 in canavanine tolerance.

microbiology↗

bioRxiv2022

Synthetic lethality between toxic amino acids, retrograde target genes and chaperones in Saccharomyces cerevisiae

The toxicity of non-proteinogenic amino acids has been known for decades. Numerous reports describe their antimicrobial/anticancer potential. However, these molecules are often toxic to the host as well, therefore a synthetic lethality approach can be beneficial. Here we investigated the potential synthetic lethality between toxic amino acids, the retrograde pathway, and molecular chaperones. In Saccharomyces cerevisiae, mitochondrial retrograde (RTG) pathway activation induces transcription of RTG-target genes, which replenishes alpha- ketoglutarate and glutamate; both metabolites are required for arginine and lysine biosynthesis. We previously reported that tolerance of canavanine, a toxic arginine derivative, requires an intact RTG pathway, and low-dose canavanine exposure reduces the expression of RTG-target genes. At higher concentrations, canavanine causes protein misfolding. Here we show that in WT, low-dose thialysine exposure, a toxic lysine analog, has a similar effect as canavanine on RTG-target gene expression. To study if single amino acid deficiency and mild protein misfolding stress elicit a similar effect on RTG-target genes, we compared expression of heat shock protein (HSP) mutants grown without arginine or lysine to WT. Arginine deprivation induces RTG-target gene expression in sse2{Delta}, hsp78{Delta}, and mdj1{Delta}, but CIT2 and DLD3 are reduced in cpr7{Delta}. Lysine deprivation has the opposite effect on RTG-target gene expression in HSP mutants. Interestingly, exposure of HSP mutants to canavanine and thialysine reversed the trend of RTG-target gene expression in several cases. The RTG-target expression pattern in HSP mutants had a predictive value in canavanine sensitivity - the mutant with the lowest expression was the most sensitive - but this was not the case for thialysine. Some, but not all, mutants in RTG-target genes are sensitive to canavanine and thialysine; additional mutation in a certain HSP can exacerbate this sensitivity. Overall, we show that inhibiting molecular chaperones, RTG-target genes, or both can sensitize cells to low doses of toxic amino acids.

genetics↗

bioRxiv2019

The response to the DNA damaging agent methyl methanesulfonate in a fungal plant pathogen

DNA damage can cause mutations that in fungal plant pathogens lead to hypervirulence and resistance to pesticides. Almost nothing is known about the response of these fungi to DNA damage. We performed transcriptomic and phosphoproteomic analyses of Fusarium oxysporum exposed to a DNA alkylating agent (MMS). At the RNA level we observe massive induction of DNA repair pathways; the most surprising is the global genome nucleotide excision repair. Cul3, Cul4, several Ubiquitin-like ligases and other components of the protein degradation machinery are significantly induced. In agreement, we observed drug synergism between a proteasome inhibitor and MMS. While our data suggest that Yap1 and Xbp1 networks are similarly activated in response to damage in yeast and Fusarium we were able to observe Fusarium specific MMS-responsive modules. These include transcription/splicing modules that are upregulated and respiration that is down-regulated. In agreement, MMS treated cells are much more sensitive to a respiration inhibitor. At the phosphoproteomic level, Adenylate cyclase, which generates cAMP, is phosphorylated by MMS and forms a network of phosphorylated proteins that include cell cycle regulators and several MAPK pathways. Recently, there are many attempts to re-sequence isolates of fungal plant pathogens. These attempts often reveal changes in the genomes that may be explained by DNA damage exposure. Our analysis provides an important starting point in understanding how these genomic changes occur.

microbiology↗