The role of Dnj4 in the transcriptional response to hydroxyurea induced DNA damage in Cryptococcus neoformans
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PROVIDER: PRJNA758105 | ENA |
REPOSITORIES: ENA
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Project description:We characterized the impact of the J domain co-chaperone, Dnj4, on the transcriptional response to DNA damage induced by hydroxyurea (an inhibitor of ribonucleotide reductase) in Cryptococcus neoformans. We treated wild type (WT) and mutant dnj4∆ log phase cells with hydroxyurea for one hour and found that the loss of DNJ4 impaired the transcriptional response to HU. In particular, the up-regulation of DNA damage and repair genes as well as iron uptake genes was impaired in these mutants. This study provides the first dataset on the transcriptional response to hydroxyurea in C. neoformans as a resource to the fungal pathogen community.
2021-12-09 | GSE182879 | GEO
Project description:Proteins which act as histone chaperones ensure genomic integrity during routine processes such as DNA replication and transcription as well as DNA repair upon damage. Herein, we identify a nuclear J domain protein, Dnj4, which interacts with histones 3 and 4 as well as Hsp71 as demonstrated in an AP-MS experiment suggesting that it integrates the heat shock chaperone machinery into histone chaperoning. In support of this, a deletion mutant lacking DNJ4 had higher levels of DNA damage than the wild type or complemented strains and was hypersensitive to DNA damaging agents. The transcriptional response to DNA damage in a mutant lacking DNJ4 was impaired. Genes related to DNA damage and iron homeostasis functions were up-regulated in the wild type strain in response to hydroxyurea treatment, however their up-regulation was either absent or reduced in a dnj4∆ mutant. Accordingly, excess iron rescued the mutant’s growth in response to hydroxyurea treatment. Iron homeostasis is crucial for virulence in Cryptococcus neoformans, however Dnj4 was found to be dispensable for virulence in a mouse model of cryptococcosis. Finally, we confirmed a conserved role of Dnj4 in histone chaperoning by expressing it in S. cerevisiae and showing that it disrupted endogenous histone chaperoning. Altogether, this study highlights the importance of a JDP co-chaperone in histone chaperoning in C. neoformans.
2021-12-15 | PXD028087 | Pride
Project description:We measured protein translation (by ribosome profiling) and RNA levels (by polyA-enriched RNA-seq) in Cryptococcus neoformans strain H99 and Cryptococcus neoformans strain JEC21. This is the first transcriptome-wide map of translation in this species complex.
2019-06-22 | GSE133125 | GEO
Project description:The target of rapamycin (TOR) pathway is an evolutionarily conserved signal transduction system that is activated by varying nutrient and environmental signals and governs a plethora of eukaryotic biological processes. Nevertheless, its role in the human fungal pathogen Cryptococcus neoformans remains elusive. In this study, we investigated the TOR pathway by functionally characterizing two Tor-like kinases, Tor1 and Tlk1, in C. neoformans. We successfully deleted TLK1, but not TOR1. TLK1 deletion did not result in any evident in vitro phenotypes, except for a minor role in diamide and polyene resistance, suggesting that Tlk1 is mainly dispensable for the growth of C. neoformans. We further demonstrated that Tor1, but not Tlk1, is essential and the target of rapamycin by constructing and analyzing conditionally regulated strains and sporulation analysis of heterozygous mutants in the diploid strain background. To analyze the functions of Tor1 in more detail, we constructed constitutive TOR1 overexpression strains. Tor1 negatively regulated thermotolerance and the DNA damage response, which are two important virulence factors of C. neoformans. We also found that TOR1 overexpression reduced Mpk1 phosphorylation, which is required for cell wall integrity and thermoresistance, and Rad53 phosphorylation, which governs the DNA damage response pathway. Tor1 is localized to the cytoplasm but enriched in the vacuole membrane. Phosphoproteomics and transcriptomics revealed that Tor1 regulates a variety of biological processes, including metabolic processes, cytoskeleton organization, ribosome biogenesis, autophagy, and stress response. Finally, screening rapamycin-sensitive and -resistant kinase and transcription factor mutants revealed that the TOR pathway may crosstalk with a number of signaling pathways, including the Hog1 pathway. In conclusion, our study demonstrates that a single Tor1 kinase plays a variety of roles in the fungal meningitis pathogen C. neoformans.
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Project description:The RNA interference (RNAi) mediated by homology-dependent degradation of the target mRNA with small RNA molecules plays a key role in controlling transcription and translation processes in a number of eukaryotic organisms. The RNAi machinery is also evolutionarily conserved in a wide variety of fungal species, including pathogenic fungi. To elucidate the physiological functions of the RNAi pathway in Cryptococcus neoformans that causes fungal meningitis, here we performed genetic analyses for genes encoding Argonaute (AGO1 and AGO2), RdRP (RDP1), and Dicers (DCR1 and DCR2) in both serotype A and D C. neoformans. The present study shows that Ago1, Rdp1, and Dcr2 are the major components of the RNAi process occurring in C. neoformans. However, the RNAi machinery is not involved in regulation of production of two virulence factors (capsule and melanin), sexual differentiation, and diverse stress response. To further gain insights into the global regulatory circuit governed by the RNAi pathway, comparative transcriptome analysis using the serotype A and D RNAi mutants was performed. Notably, an increase in transcript abundance of active transposons, such as T2 and T3, was observed in the rdp1? mutant. Therefore, this study can improve our understanding of the role of the RNAi genes in human fungal pathogens including C. neoformans. This SuperSeries is composed of the following subset Series: GSE21176: Molecular and Functional Characterization of the role of RNA silencing components in Cryptococcus neoformans [RNAi_Serotype A] GSE21177: Molecular and Functional Characterization of the role of RNA silencing components in Cryptococcus neoformans [RNAi_Serotype D] Refer to individual Series
2010-05-01 | E-GEOD-21178 | biostudies-arrayexpress
Project description:We investigated the effects of the hypoxia-mimetic CoCl2 on the gene expression of pathogenic fungus Cryptococcus neoformans. Keywords: compound treatment design
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Project description:Cryptococcus neoformans interactions with murine macrophages are critical for disease. In this project we analyzed fungal proteins which were co-purified with murine host proteins after interaction. H99 C. neoformans was opsonized with mAb 18B7 and addedd to murine macrophages. Then murine cells were lysed and cell extracts submitted to proteomics.
2023-03-11 | PXD024951 | Pride
Project description:Light is a universal environmental signal perceived by many organisms, including the fungi in which light regulates both common and unique biological processes depending on the species. We conducted a whole-genome microarray analysis on the basidiomycete fungus Cryptococcus neoformans to identify light-regulated genes.
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Project description:Proper mitochondrial function is critical for the ability of the fungal pathogen Cryptococcus neoformans to cause disease. Mitochondrial dysfunction of WT cells treated with antimycin A or L-DOPA, or on cells lacking Cir1 is evident from this dataset. These experiments revealed influences on transcript levels of genes encoding Fe-S cluster assembly components and the response to oxidative stress in Cryptococcus neoformans.
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Project description:Cryptococcus neoformans lab strain H99 was used to obtain brefeldin A adaptors. Transcriptomes of 4 adaptors, each bearing a unique aneuploid, were compared to H99.
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