scholarly journals Urmylation: A Ubiquitin-like Pathway that Functions during Invasive Growth and Budding in Yeast

2003 ◽  
Vol 14 (11) ◽  
pp. 4329-4341 ◽  
Author(s):  
April S. Goehring ◽  
David M. Rivers ◽  
George F. Sprague
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Growth ◽  
Genetic Interaction ◽  
Nutrient Sensing ◽  
Genetic Interactions ◽  
Invasive Growth ◽  
Tor Pathway ◽  
Molecular Functions ◽  
Simultaneous Loss ◽  
P21 Activated Kinase

Ubiquitin is a small modifier protein that is conjugated to substrates to target them for degradation. Recently, a surprising number of ubiquitin-like proteins have been identified that also can be attached to proteins. Herein, we identify two molecular functions for the posttranslational protein modifier from Saccharomyces cerevisiae, Urm1p. Simultaneous loss of Urm1p and Cla4p, a p21-activated kinase that functions in budding, is lethal. This result suggests a role for the urmylation pathway in budding. Furthermore, loss of the urmylation pathway causes defects in invasive growth and confers sensitivity to rapamycin. Our results indicate that the sensitivity to rapamycin is due to a genetic interaction with the TOR pathway, which is important for regulation of cell growth in response to nutrients. We have found that Urm1p can be attached to a number of proteins. Loss of five genes that are also essential in a cla4Δ strain, NCS2, NCS6, ELP2, ELP6, and URE2, affect the level of at least one Urm1p conjugate. Moreover, these five genes have a role in invasive growth and display genetic interactions with the TOR pathway. In summary, our results suggest the urmylation pathway is involved in nutrient sensing and budding.

scholarly journals Genome-wide mapping of unexplored essential regions in the Saccharomyces cerevisiae genome: evidence for hidden synthetic lethal combinations in a genetic interaction network

2014 ◽  
Vol 42 (15) ◽  
pp. 9838-9853 ◽  
Author(s):  
Saeed Kaboli ◽  
Takuya Yamakawa ◽  
Keisuke Sunada ◽  
Tao Takagaki ◽  
Yu Sasano ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Genetic Interaction ◽  
Interaction Network ◽  
Essential Genes ◽  
Genetic Interactions ◽  
Lethal Gene ◽  
Synthetic Lethal ◽  
Genome Wide ◽  
A Genome ◽  
Wide Scale

Abstract Despite systematic approaches to mapping networks of genetic interactions in Saccharomyces cerevisiae, exploration of genetic interactions on a genome-wide scale has been limited. The S. cerevisiae haploid genome has 110 regions that are longer than 10 kb but harbor only non-essential genes. Here, we attempted to delete these regions by PCR-mediated chromosomal deletion technology (PCD), which enables chromosomal segments to be deleted by a one-step transformation. Thirty-three of the 110 regions could be deleted, but the remaining 77 regions could not. To determine whether the 77 undeletable regions are essential, we successfully converted 67 of them to mini-chromosomes marked with URA3 using PCR-mediated chromosome splitting technology and conducted a mitotic loss assay of the mini-chromosomes. Fifty-six of the 67 regions were found to be essential for cell growth, and 49 of these carried co-lethal gene pair(s) that were not previously been detected by synthetic genetic array analysis. This result implies that regions harboring only non-essential genes contain unidentified synthetic lethal combinations at an unexpectedly high frequency, revealing a novel landscape of genetic interactions in the S. cerevisiae genome. Furthermore, this study indicates that segmental deletion might be exploited for not only revealing genome function but also breeding stress-tolerant strains.

scholarly journals The Tor Pathway Regulates Gene Expression by Linking Nutrient Sensing to Histone Acetylation

2003 ◽  
Vol 23 (2) ◽  
pp. 629-635 ◽  
Author(s):  
John R. Rohde ◽  
Maria E. Cardenas
Keyword(s):  
Gene Expression ◽  
Cell Growth ◽  
Histone Acetylation ◽  
Nutrient Sensing ◽  
Gene Promoters ◽  
Histone H4 ◽  
Tor Pathway ◽  
Histone H4 Acetylation ◽  
Promoter Occupancy ◽  
Histone H4 Deacetylation

ABSTRACT The Tor pathway mediates cell growth in response to nutrient availability, in part by inducing ribosomal protein (RP) gene expression via an unknown mechanism. Expression of RP genes coincides with recruitment of the Esa1 histone acetylase to RP gene promoters. We show that inhibition of Tor with rapamycin releases Esa1 from RP gene promoters and leads to histone H4 deacetylation without affecting promoter occupancy by Rap1 and Abf1. Genetic and biochemical evidence identifies Rpd3 as the major histone deacetylase responsible for reversing histone H4 acetylation at RP gene promoters in response to Tor inhibition by rapamycin or nutrient limitation. Our results illustrate that the Tor pathway links nutrient sensing with histone acetylation to control RP gene expression and cell growth.

scholarly journals Chemical-Genetic Interactions with the Proline Analog L-Azetidine-2-Carboxylic Acid in Saccharomyces cerevisiae

2020 ◽  
Vol 10 (12) ◽  
pp. 4335-4345
Author(s):  
Matthew D. Berg ◽  
Yanrui Zhu ◽  
Joshua Isaacson ◽  
Julie Genereaux ◽  
Raphaël Loll-Krippleber ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Amino Acid ◽  
Carboxylic Acid ◽  
Cellular Response ◽  
Protein Quality ◽  
Genetic Interaction ◽  
Genetic Interactions ◽  
Temperature Sensitive ◽  
Chemical Genetic ◽  
Proteotoxic Stress

Non-proteinogenic amino acids, such as the proline analog L-azetidine-2-carboxylic acid (AZC), are detrimental to cells because they are mis-incorporated into proteins and lead to proteotoxic stress. Our goal was to identify genes that show chemical-genetic interactions with AZC in Saccharomyces cerevisiae and thus also potentially define the pathways cells use to cope with amino acid mis-incorporation. Screening the yeast deletion and temperature sensitive collections, we found 72 alleles with negative chemical-genetic interactions with AZC treatment and 12 alleles that suppress AZC toxicity. Many of the genes with negative chemical-genetic interactions are involved in protein quality control pathways through the proteasome. Genes involved in actin cytoskeleton organization and endocytosis also had negative chemical-genetic interactions with AZC. Related to this, the number of actin patches per cell increases upon AZC treatment. Many of the same cellular processes were identified to have interactions with proteotoxic stress caused by two other amino acid analogs, canavanine and thialysine, or a mistranslating tRNA variant that mis-incorporates serine at proline codons. Alleles that suppressed AZC-induced toxicity functioned through the amino acid sensing TOR pathway or controlled amino acid permeases required for AZC uptake. Further suggesting the potential of genetic changes to influence the cellular response to proteotoxic stress, overexpressing many of the genes that had a negative chemical-genetic interaction with AZC suppressed AZC toxicity.

scholarly journals RECOMBINATION BETWEEN GENES LOCATED ON NONHOMOLOGOUS CHROMOSOMES IN SACCHAROMYCES CEREVISIAE

Genetics ◽  
1982 ◽  
Vol 101 (3-4) ◽  
pp. 369-404
Author(s):  
Margaret Dubay Mikus ◽  
Thomas D Petes
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Genetic Interaction ◽  
Common Type ◽  
Genetic Interactions ◽  
The Other ◽  
Physical Analysis ◽  
Ura3 Gene ◽  
Leu2 Gene ◽  
Transfer Of Information ◽  
Repeated Genes

ABSTRACT We constructed strains of Saccharomyces cerevisiae that contained two different mutant alleles of either the leu2 gene or the ura3 gene. These repeated genes were located on nonhomologous chromosomes; the two ura3- alleles were located on chromosomes V and XII and the two leu2- alleles were located on chromosomes III and XII. Genetic interactions between the two mutant copies of a gene were detected by the generation of either Leu+ or Ura+ revertants. Both spontaneous and ultraviolet irradiation-induced revertants were examined. By genetic and physical analysis, we have shown that Leu+ or Ura+ revertants can arise by a variety of different genetic interactions. The most common type of genetic interaction is the nonreciprocal transfer of information from one repeat to the other. We also detected reciprocal recombination between repeated genes, resulting in reciprocally translocated chromosomes.

scholarly journals Mutations in the SAC1 gene suppress defects in yeast Golgi and yeast actin function.

1989 ◽  
Vol 109 (6) ◽  
pp. 2939-2950 ◽  
Author(s):  
A E Cleves ◽  
P J Novick ◽  
V A Bankaitis
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Growth ◽  
Secretory Pathway ◽  
Genetic Data ◽  
Secretory Vesicle ◽  
Genetic Interactions ◽  
Spatial Regulation ◽  
Allele Specific ◽  
Regulation Of Secretion ◽  
High Degree

The budding mode of Saccharomyces cerevisiae cell growth demands that a high degree of secretory polarity be established and directed toward the emerging bud. We report here our demonstration that mutations in SAC1, a gene identified by virtue of its allele-specific genetic interactions with yeast actin defects, were also capable of suppressing sec14 lethalities associated with yeast Golgi defects. Moreover, these sac1 suppressor properties also extended to sec6 and sec9 secretory vesicle defects. The genetic data are consistent with the notion that SAC1p modulates both secretory pathway and actin cytoskeleton function. On this basis, we suggest that SAC1p may represent one aspect of the mechanism whereby secretory and cytoskeletal activities are coordinated, so that proper spatial regulation of secretion might be achieved.

scholarly journals Identification and Characterization of Rapidly Accumulating sch9Δ Suppressor Mutations in Saccharomyces cerevisiae

2021 ◽  
Author(s):  
Patricia P Peterson ◽  
Zhengchang Liu
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Transcription Factors ◽  
Cell Growth ◽  
Carbon Sources ◽  
Nutrient Sensing ◽  
Suppressor Mutations ◽  
Genes Encoding ◽  
Mutant Phenotypes ◽  
Pka Pathway

Abstract Nutrient sensing is important for cell growth, aging, and longevity. In Saccharomyces cerevisiae, Sch9, an AGC-family protein kinase, is a major nutrient sensing kinase homologous to mammalian Akt and S6 kinase. Sch9 integrates environmental cues with cell growth by functioning downstream of TORC1 and in parallel with the Ras/PKA pathway. Mutations in SCH9 lead to reduced cell growth in dextrose medium; however, reports on the ability of sch9Δ mutants to utilize non-fermentable carbon sources are inconsistent. Here we show that sch9Δ mutant strains cannot grow on non-fermentable carbon sources and rapidly accumulate suppressor mutations, which reverse growth defects of sch9Δ mutants. sch9Δ induces gene expression of three transcription factors required for utilization of non-fermentable carbon sources, Cat8, Adr1, and Hap4, while sch9Δ suppressor mutations, termed sns1 and sns2, strongly decrease the gene expression of those transcription factors. Despite the genetic suppression interactions, both sch9Δ and sns1 (or sns2) homozygous mutants have severe defects in meiosis. By screening mutants defective in sporulation, we identified additional sch9Δ suppressor mutants with mutations in GPB1, GPB2, and MCK1. Using library complementation and genetic analysis, we identified SNS1 and SNS2 to be IRA2 and IRA1, respectively. Furthermore, we discovered that lifespan extension in sch9Δ mutants is dependent on IRA2 and that PKA inactivation greatly increases basal expression of CAT8, ADR1, and HAP4. Our results demonstrate that sch9Δ leads to complete loss of growth on non-fermentable carbon sources and mutations in MCK1 or genes encoding negative regulators of the Ras/PKA pathway reverse sch9Δ mutant phenotypes.

Genetic Interactions Effects of Cardiovascular Disorder Using Computational Models: A Review

2020 ◽  
Vol 9 (3) ◽  
pp. 177-191
Author(s):  
Sridharan Priya ◽  
Radha K. Manavalan
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Cardiovascular Diseases ◽  
Computational Models ◽  
Genetic Interaction ◽  
Association Studies ◽  
Genetic Interactions ◽  
Computational Techniques ◽  
Genome Wide Association Studies ◽  
Artery Disease

Background: The diseases in the heart and blood vessels such as heart attack, Coronary Artery Disease, Myocardial Infarction (MI), High Blood Pressure, and Obesity, are generally referred to as Cardiovascular Diseases (CVD). The risk factors of CVD include gender, age, cholesterol/ LDL, family history, hypertension, smoking, and genetic and environmental factors. Genome- Wide Association Studies (GWAS) focus on identifying the genetic interactions and genetic architectures of CVD. Objective: Genetic interactions or Epistasis infer the interactions between two or more genes where one gene masks the traits of another gene and increases the susceptibility of CVD. To identify the Epistasis relationship through biological or laboratory methods needs an enormous workforce and more cost. Hence, this paper presents the review of various statistical and Machine learning approaches so far proposed to detect genetic interaction effects for the identification of various Cardiovascular diseases such as Coronary Artery Disease (CAD), MI, Hypertension, HDL and Lipid phenotypes data, and Body Mass Index dataset. Conclusion: This study reveals that various computational models identified the candidate genes such as AGT, PAI-1, ACE, PTPN22, MTHR, FAM107B, ZNF107, PON1, PON2, GTF2E1, ADGRB3, and FTO, which play a major role in genetic interactions for the causes of CVDs. The benefits, limitations, and issues of the various computational techniques for the evolution of epistasis responsible for cardiovascular diseases are exhibited.

scholarly journals Stress Mediating Genes in Aging, Health, and Longevity Traits: Effects of Multiple Interactions

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 286-286
Author(s):  
Anatoliy Yashin ◽  
Dequing Wu ◽  
Konstantin Arbeev ◽  
Arseniy Yashkin ◽  
Galina Gorbunova ◽  
...  
Keyword(s):  
Strong Interaction ◽  
Genetic Interaction ◽  
Interaction Effects ◽  
Genetic Interactions ◽  
Risk Scores ◽  
Data Sets ◽  
Interaction Patterns ◽  
Polygenic Risk ◽  
Drug Candidates ◽  
Aging Health

Abstract Persistent stress of external or internal origin accelerates aging, increases risk of aging related health disorders, and shortens lifespan. Stressors activate stress response genes, and their products collectively influence traits. The variability of stressors and responses to them contribute to trait heterogeneity, which may cause the failure of clinical trials for drug candidates. The objectives of this paper are: to address the heterogeneity issue; to evaluate collective interaction effects of genetic factors on Alzheimer’s disease (AD) and longevity using HRS data; to identify differences and similarities in patterns of genetic interactions within two genders; and to compare AD related genetic interaction patterns in HRS and LOADFS data. To reach these objectives we: selected candidate genes from stress related pathways affecting AD/longevity; implemented logistic regression model with interaction term to evaluate effects of SNP-pairs on these traits for males and females; constructed the novel interaction polygenic risk scores for SNPs, which showed strong interaction potential, and evaluated effects of these scores on AD/longevity; and compared patterns of genetic interactions within the two genders and within two datasets. We found there were many genes involved in highly significant interactions that were the same and that were different within the two genders. The effects of interaction polygenic risk scores on AD were strong and highly statistically significant. These conclusions were confirmed in analyses of interaction effects on longevity trait using HRS data. Comparison of HRS to LOADFS data showed that many genes had strong interaction effects on AD in both data sets.

scholarly journals Shared Components of the FRQ-Less Oscillator and TOR Pathway Maintain Rhythmicity in Neurospora

2021 ◽  
pp. 074873042199994
Author(s):  
Rosa Eskandari ◽  
Lalanthi Ratnayake ◽  
Patricia L. Lakin-Thomas
Keyword(s):  
Circadian Rhythms ◽  
Clock Genes ◽  
Nutrient Sensing ◽  
Mass Spectrometry Analysis ◽  
Growth Responses ◽  
Tor Pathway ◽  
Spectrometry Analysis ◽  
Binding Partner ◽  
Binding Partners ◽  
Free Running

Molecular models for the endogenous oscillators that drive circadian rhythms in eukaryotes center on rhythmic transcription/translation of a small number of “clock genes.” Although substantial evidence supports the concept that negative and positive transcription/translation feedback loops (TTFLs) are responsible for regulating the expression of these clock genes, certain rhythms in the filamentous fungus Neurospora crassa continue even when clock genes ( frq, wc-1, and wc-2) are not rhythmically expressed. Identification of the rhythmic processes operating outside of the TTFL has been a major unresolved area in circadian biology. Our lab previously identified a mutation ( vta) that abolishes FRQ-less rhythmicity of the conidiation rhythm and also affects rhythmicity when FRQ is functional. Further studies identified the vta gene product as a component of the TOR (Target of Rapamycin) nutrient-sensing pathway that is conserved in eukaryotes. We now report the discovery of TOR pathway components including GTR2 (homologous to the yeast protein Gtr2, and RAG C/D in mammals) as binding partners of VTA through co-immunoprecipitation (IP) and mass spectrometry analysis using a VTA-FLAG strain. Reciprocal IP with GTR2-FLAG found VTA as a binding partner. A Δ gtr2 strain was deficient in growth responses to amino acids. Free-running conidiation rhythms in a FRQ-less strain were abolished in Δ gtr2. Entrainment of a FRQ-less strain to cycles of heat pulses demonstrated that Δ gtr2 is defective in entrainment. In all of these assays, Δ gtr2 is similar to Δ vta. In addition, expression of GTR2 protein was found to be rhythmic across two circadian cycles, and functional VTA was required for GTR2 rhythmicity. FRQ protein exhibited the expected rhythm in the presence of GTR2 but the rhythmic level of FRQ dampened in the absence of GTR2. These results establish association of VTA with GTR2, and their role in maintaining functional circadian rhythms through the TOR pathway.

scholarly journals Suppressor Analysis of the Saccharomyces cerevisiae Gene REC104 Reveals a Genetic Interaction With REC102

Genetics ◽  
1999 ◽  
Vol 151 (4) ◽  
pp. 1261-1272 ◽  
Author(s):  
Laura Salem ◽  
Natalie Walter ◽  
Robert Malone
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Meiotic Recombination ◽  
Null Allele ◽  
Genetic Interaction ◽  
In Vitro Mutagenesis ◽  
Conditional Mutations ◽  
Suppressor Analysis

Abstract REC104 is a gene required for the initiation of meiotic recombination in Saccharomyces cerevisiae. To better understand the role of REC104 in meiosis, we used an in vitro mutagenesis technique to create a set of temperature-conditional mutations in REC104 and used one ts allele (rec104-8) in a screen for highcopy suppressors. An increased dosage of the early exchange gene REC102 was found to suppress the conditional recombinational reduction in rec104-8 as well as in several other conditional rec104 alleles. However, no suppression was observed for a null allele of REC104, indicating that the suppression by REC102 is not “bypass” suppression. Overexpression of the early meiotic genes REC114, RAD50, HOP1, and RED1 fails to suppress any of the rec104 conditional alleles, indicating that the suppression might be specific to REC102.

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