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Full-Text Articles in Medicine and Health Sciences
Signaling Through Lrg1, Rho1 And Pkc1 Governs Candida Albicans Morphogenesis In Response To Diverse Cues, Jinglin L. Xie, Nora Grahl, Trevor Sless, Michelle Leach, Sang Hu Kim, Deborah Hogan
Signaling Through Lrg1, Rho1 And Pkc1 Governs Candida Albicans Morphogenesis In Response To Diverse Cues, Jinglin L. Xie, Nora Grahl, Trevor Sless, Michelle Leach, Sang Hu Kim, Deborah Hogan
Dartmouth Scholarship
The capacity to transition between distinct morphological forms is a key virulence trait for diverse fungal pathogens. A poignant example of a leading opportunistic fungal pathogen of humans for which an environmentally responsive developmental program underpins virulence is Candida albicans. C. albicans mutants that are defective in the transition between yeast and filamentous forms typically have reduced virulence. Although many positive regulators of C. albicans filamentation have been defined, there are fewer negative regulators that have been implicated in repression of filamentation in the absence of inducing cues. To discover novel negative regulators of filamentation, we screened …
Sec17 Can Trigger Fusion Of Trans-Snare Paired Membranes Without Sec18, Michael Zick, Amy Orr, Matthew L. Schwartz, Alexey J. Merz, William Wickner
Sec17 Can Trigger Fusion Of Trans-Snare Paired Membranes Without Sec18, Michael Zick, Amy Orr, Matthew L. Schwartz, Alexey J. Merz, William Wickner
Dartmouth Scholarship
Sec17 [soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein; α-SNAP] and Sec18 (NSF) perform ATP-dependent disassembly of cis-SNARE complexes, liberating SNAREs for subsequent assembly of trans-complexes for fusion. A mutant of Sec17, with limited ability to stimulate Sec18, still strongly enhanced fusion when ample Sec18 was supplied, suggesting that Sec17 has additional functions. We used fusion reactions where the four SNAREs were initially separate, thus requiring no disassembly by Sec18. With proteoliposomes bearing asymmetrically disposed SNAREs, tethering and trans-SNARE pairing allowed slow fusion. Addition of Sec17 did not affect the levels of trans-SNARE complex but triggered sudden fusion of trans-SNARE paired proteoliposomes. …
Fungal Mediator Tail Subunits Contain Classical Transcriptional Activation Domains, Zhongle Liu, Lawrence C. Myers
Fungal Mediator Tail Subunits Contain Classical Transcriptional Activation Domains, Zhongle Liu, Lawrence C. Myers
Dartmouth Scholarship
Classical activation domains within DNA-bound eukaryotic transcription factors make weak interactions with coactivator complexes, such as Mediator, to stimulate transcription. How these interactions stimulate transcription, however, is unknown. The activation of reporter genes by artificial fusion of Mediator subunits to DNA binding domains that bind to their promoters has been cited as evidence that the primary role of activators is simply to recruit Mediator. We have identified potent classical transcriptional activation domains in the C termini of several tail module subunits of Saccharomyces cerevisiae, Candida albicans, and Candida dubliniensis Mediator, while their N-terminal domains are necessary and sufficient for their …
Analysis Of Clock-Regulated Genes In Neurospora Reveals Widespread Posttranscriptional Control Of Metabolic Potential, Jennifer M. M. Hurley, Arko Dasgupta, Jillian M. Emerson, Xiaoying Zhou, Carol S. Ringelberg, Nicole Knabe
Analysis Of Clock-Regulated Genes In Neurospora Reveals Widespread Posttranscriptional Control Of Metabolic Potential, Jennifer M. M. Hurley, Arko Dasgupta, Jillian M. Emerson, Xiaoying Zhou, Carol S. Ringelberg, Nicole Knabe
Dartmouth Scholarship
Neurospora crassa has been for decades a principal model for filamentous fungal genetics and physiology as well as for understanding the mechanism of circadian clocks. Eukaryotic fungal and animal clocks comprise transcription-translation-based feedback loops that control rhythmic transcription of a substantial fraction of these transcriptomes, yielding the changes in protein abundance that mediate circadian regulation of physiology and metabolism: Understanding circadian control of gene expression is key to understanding eukaryotic, including fungal, physiology. Indeed, the isolation of clock-controlled genes (ccgs) was pioneered in Neurospora where circadian output begins with binding of the core circadian transcription factor WCC to a subset …
Chip-Seq And In Vivo Transcriptome Analyses Of The Aspergillus Fumigatus Srebp Srba Reveals A New Regulator Of The Fungal Hypoxia Response And Virulence, Dawoon Chung, Bridget M. Barker, Charles C. Carey, Brittney Merriman
Chip-Seq And In Vivo Transcriptome Analyses Of The Aspergillus Fumigatus Srebp Srba Reveals A New Regulator Of The Fungal Hypoxia Response And Virulence, Dawoon Chung, Bridget M. Barker, Charles C. Carey, Brittney Merriman
Dartmouth Scholarship
The Aspergillus fumigatus sterol regulatory element binding protein (SREBP) SrbA belongs to the basic Helix-Loop-Helix (bHLH) family of transcription factors and is crucial for antifungal drug resistance and virulence. The latter phenotype is especially striking, as loss of SrbA results in complete loss of virulence in murine models of invasive pulmonary aspergillosis (IPA). How fungal SREBPs mediate fungal virulence is unknown, though it has been suggested that lack of growth in hypoxic conditions accounts for the attenuated virulence. To further understand the role of SrbA in fungal infection site pathobiology, chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq) was …
The Fungal Pathogen Aspergillus Fumigatus Regulates Growth, Metabolism, And Stress Resistance In Response To Light, Kevin K. Fuller, Carol S. Ringelberg, Jennifer J. Loros, Jay C. Dunlap
The Fungal Pathogen Aspergillus Fumigatus Regulates Growth, Metabolism, And Stress Resistance In Response To Light, Kevin K. Fuller, Carol S. Ringelberg, Jennifer J. Loros, Jay C. Dunlap
Dartmouth Scholarship
Light is a pervasive environmental factor that regulates development, stress resistance, and even virulence in numerous fungal species. Though much research has focused on signaling pathways in Aspergillus fumigatus, an understanding of how this pathogen responds to light is lacking. In this report, we demonstrate that the fungus does indeed respond to both blue and red portions of the visible spectrum. Included in the A. fumigatus light response is a reduction in conidial germination rates, increased hyphal pigmentation, enhanced resistance to acute ultraviolet and oxidative stresses, and an increased susceptibility to cell wall perturbation. By performing gene deletion analyses, we …
Mediator Influences Telomeric Silencing And Cellular Life Span, Xuefeng Zhu, Beidong Liu, Jonas O. P. Carlsten, Jenny Beve, Thomas Nyström, Lawrence C. Myers, Claes M. Gustafsson
Mediator Influences Telomeric Silencing And Cellular Life Span, Xuefeng Zhu, Beidong Liu, Jonas O. P. Carlsten, Jenny Beve, Thomas Nyström, Lawrence C. Myers, Claes M. Gustafsson
Dartmouth Scholarship
The Mediator complex is required for the regulated transcription of nearly all RNA polymerase II-dependent genes. Here we demonstrate a new role for Mediator which appears to be separate from its function as a transcriptional coactivator. Mediator associates directly with heterochromatin at telomeres and influences the exact boundary between active and inactive chromatin. Loss of the Mediator Med5 subunit or mutations in Med7 cause a depletion of the complex from regions located near subtelomeric X elements, which leads to a change in the balance between the Sir2 and Sas2 proteins. These changes in turn result in increased levels of H4K16 …
Circadian Clock-Specific Roles For The Light Response Protein White Collar-2, Michael A. Collett, Jay C. Dunlap, Jennifer J. Loros
Circadian Clock-Specific Roles For The Light Response Protein White Collar-2, Michael A. Collett, Jay C. Dunlap, Jennifer J. Loros
Dartmouth Scholarship
To understand the role of white collar-2 in theNeurospora circadian clock, we examined alleles ofwc-2 thought to encode partially functional proteins. We found that wc-2 allele ER24 contained a conservative mutation in the zinc finger. This mutation results in reduced levels of circadian rhythm-critical clock gene products, frq mRNA and FRQ protein, and in a lengthened period of the circadian clock. In addition, this mutation altered a second canonical property of the clock, temperature compensation: as temperature increased, period length decreased substantially. This temperature compensation defect correlated with a temperature-dependent increase in overall FRQ protein levels, with the …
The Gtp-Bound Form Of The Yeast Ran/Tc4 Homologue Blocks Nuclear Protein Import And Appearance Of Poly(A)+ Rna In The Cytoplasm., Gabriel Schlenstedt, Claudio Saavedra, Jonathan D. Loeb, Charles N. Cole, Pamela A. Silver
The Gtp-Bound Form Of The Yeast Ran/Tc4 Homologue Blocks Nuclear Protein Import And Appearance Of Poly(A)+ Rna In The Cytoplasm., Gabriel Schlenstedt, Claudio Saavedra, Jonathan D. Loeb, Charles N. Cole, Pamela A. Silver
Dartmouth Scholarship
Ran/TC4, a Ras-like GTP-binding protein, and its nucleotide exchanger, RCC1, have been implicated in control of protein movement into the nucleus and cytoplasmic accumulation of mRNA. Saccharomyces cerevisiae contains two homologues of the mammalian Ran/TC4, encoded by the GSP1 and GSP2 genes. We have constructed yeast strains that overproduce either wild-type Gsp1 or a form of Gsp1 with glycine-21 converted to valine (Gsp1-G21V), which we show stabilizes the GTP-bound form. Cells producing Gsp1-G21V have defects in localization of nuclear proteins; nuclear proteins accumulate in the cytoplasm following galactose induction of Gsp1-G21V. Similarly, cells producing Gsp1-G21V retain poly(A)+ RNA in their …
Characterization Of The Formate (For) Locus, Which Encodes The Cytosolic Serine Hydroxymethyltransferase Of Neurospora Crassa., C. Robertson Mcclung, Cynthia R. Davis, Karen M. Page, Sylvia A. Denome
Characterization Of The Formate (For) Locus, Which Encodes The Cytosolic Serine Hydroxymethyltransferase Of Neurospora Crassa., C. Robertson Mcclung, Cynthia R. Davis, Karen M. Page, Sylvia A. Denome
Dartmouth Scholarship
Serine hydroxymethyltransferase (SHMT) occupies a central position in one-carbon (C1) metabolism, catalyzing the reaction of serine and tetrahydrofolate to yield glycine and 5,10-methylenetetrahydrofolate. Methylenetetrahydrofolate serves as a donor of C1 units for the synthesis of numerous compounds, including purines, thymidylate, lipids, and methionine. We provide evidence that the formate (for) locus of Neurospora crassa encodes cytosolic SHMT. The for+ gene was localized to a 2.8-kb BglII fragment by complementation (restoration to formate-independent growth) of a strain carrying a recessive for allele, which confers a growth requirement for formate. The for+ gene encodes a polypeptide of 479 amino acids which shows …