scholarly journals A Genome-Wide Screen in Saccharomyces cerevisiae Reveals a Critical Role for Oxidative Phosphorylation in Cellular Tolerance to Lithium Hexafluorophosphate

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 888
Author(s):  
Xuejiao Jin ◽  
Jie Zhang ◽  
Tingting An ◽  
Huihui Zhao ◽  
Wenhao Fu ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Oxidative Phosphorylation ◽  
Cellular Response ◽  
Critical Role ◽  
Lithium Ion ◽  
Deletion Mutants ◽  
High Concentration ◽  
Genome Wide ◽  
A Genome ◽  
Lithium Hexafluorophosphate

Lithium hexafluorophosphate (LiPF6) is one of the leading electrolytes in lithium-ion batteries, and its usage has increased tremendously in the past few years. Little is known, however, about its potential environmental and biological impacts. In order to improve our understanding of the cytotoxicity of LiPF6 and the specific cellular response mechanisms to it, we performed a genome-wide screen using a yeast (Saccharomyces cerevisiae) deletion mutant collection and identified 75 gene deletion mutants that showed LiPF6 sensitivity. Among these, genes associated with mitochondria showed the most enrichment. We also found that LiPF6 is more toxic to yeast than lithium chloride (LiCl) or sodium hexafluorophosphate (NaPF6). Physiological analysis showed that a high concentration of LiPF6 caused mitochondrial damage, reactive oxygen species (ROS) accumulation, and ATP content changes. Compared with the results of previous genome-wide screening for LiCl-sensitive mutants, we found that oxidative phosphorylation-related mutants were specifically hypersensitive to LiPF6. In these deletion mutants, LiPF6 treatment resulted in higher ROS production and reduced ATP levels, suggesting that oxidative phosphorylation-related genes were important for counteracting LiPF6-induced toxicity. Taken together, our results identified genes specifically involved in LiPF6-modulated toxicity, and demonstrated that oxidative stress and ATP imbalance maybe the driving factors in governing LiPF6-induced toxicity.

scholarly journals A genome-wide screen in Saccharomyces cerevisiae reveals a critical role for the mitochondria in the toxicity of a trichothecene mycotoxin

2009 ◽  
Vol 106 (51) ◽  
pp. 21883-21888 ◽  
Author(s):  
J. E. McLaughlin ◽  
M. A. Bin-Umer ◽  
A. Tortora ◽  
N. Mendez ◽  
S. McCormick ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Critical Role ◽  
Trichothecene Mycotoxin ◽  
Genome Wide ◽  
A Genome

scholarly journals A genome-wide screen for Saccharomyces cerevisiae deletion mutants that affect telomere length

2004 ◽  
Vol 101 (23) ◽  
pp. 8658-8663 ◽  
Author(s):  
S. H. Askree ◽  
T. Yehuda ◽  
S. Smolikov ◽  
R. Gurevich ◽  
J. Hawk ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Telomere Length ◽  
Deletion Mutants ◽  
Genome Wide ◽  
A Genome

scholarly journals Genome-wide identification of cyclin-dependent kinase (CDK) genes affecting adipocyte differentiation in cattle

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Cuili Pan ◽  
Zhaoxiong Lei ◽  
Shuzhe Wang ◽  
Xingping Wang ◽  
Dawei Wei ◽  
...  
Keyword(s):  
Gene Family ◽  
Expression Analysis ◽  
Adipocyte Differentiation ◽  
Bos Taurus ◽  
Adipogenic Differentiation ◽  
Critical Role ◽  
Bos Indicus ◽  
Specific Expression ◽  
Genome Wide ◽  
A Genome

Abstract Background Cyclin-dependent kinases (CDKs) are protein kinases regulating important cellular processes such as cell cycle and transcription. Many CDK genes also play a critical role during adipogenic differentiation, but the role of CDK gene family in regulating bovine adipocyte differentiation has not been studied. Therefore, the present study aims to characterize the CDK gene family in bovine and study their expression pattern during adipocyte differentiation. Results We performed a genome-wide analysis and identified a number of CDK genes in several bovine species. The CDK genes were classified into 8 subfamilies through phylogenetic analysis. We found that 25 bovine CDK genes were distributed in 16 different chromosomes. Collinearity analysis revealed that the CDK gene family in Bos taurus is homologous with Bos indicus, Hybrid-Bos taurus, Hybrid Bos indicus, Bos grunniens and Bubalus bubalis. Several CDK genes had higher expression levels in preadipocytes than in differentiated adipocytes, as shown by RNA-seq analysis and qPCR, suggesting a role in the growth of emerging lipid droplets. Conclusion In this research, 185 CDK genes were identified and grouped into eight distinct clades in Bovidae, showing extensively homology. Global expression analysis of different bovine tissues and specific expression analysis during adipocytes differentiation revealed CDK4, CDK7, CDK8, CDK9 and CDK14 may be involved in bovine adipocyte differentiation. The results provide a basis for further study to determine the roles of CDK gene family in regulating adipocyte differentiation, which is beneficial for beef quality improvement.

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.

Pleiotropic drug-resistance attenuated genomic library improves elucidation of drug mechanisms

2015 ◽  
Vol 11 (11) ◽  
pp. 3129-3136 ◽  
Author(s):  
Namal V. C. Coorey ◽  
James H. Matthews ◽  
David S. Bellows ◽  
Paul H. Atkinson
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Drug Resistance ◽  
Mechanism Of Action ◽  
Gene Deletion ◽  
Genomic Library ◽  
Deletion Mutants ◽  
Pleiotropic Drug Resistance ◽  
Genome Wide

Identifying Saccharomyces cerevisiae genome-wide gene deletion mutants that confer hypersensitivity to a xenobiotic aids the elucidation of its mechanism of action (MoA).

scholarly journals The S1/S2 boundary of SARS-CoV-2 spike protein modulates cell entry pathways and transmission

2020 ◽  
Author(s):  
Yunkai Zhu ◽  
Fei Feng ◽  
Gaowei Hu ◽  
Yuyan Wang ◽  
Yin Yu ◽  
...  
Keyword(s):  
Critical Role ◽  
Surface Expression ◽  
Spike Protein ◽  
Hamster Model ◽  
Entry Pathway ◽  
Genome Wide ◽  
A Genome ◽  
Model Animal ◽  
Public Health Challenges

SUMMARYThe global spread of SARS-CoV-2 is posing major public health challenges. One unique feature of SARS-CoV-2 spike protein is the insertion of multi-basic residues at the S1/S2 subunit cleavage site, the function of which remains uncertain. We found that the virus with intact spike (Sfull) preferentially enters cells via fusion at the plasma membrane, whereas a clone (Sdel) with deletion disrupting the multi-basic S1/S2 site instead utilizes a less efficient endosomal entry pathway. This idea was supported by the identification of a suite of endosomal entry factors specific to Sdel virus by a genome-wide CRISPR-Cas9 screen. A panel of host factors regulating the surface expression of ACE2 was identified for both viruses. Using a hamster model, animal-to-animal transmission with the Sdel virus was almost completely abrogated, unlike with Sfull. These findings highlight the critical role of the S1/S2 boundary of the SARS-CoV-2 spike protein in modulating virus entry and transmission.

scholarly journals Mitochondria-encoded genes contribute to evolution of heat and cold tolerance in yeast

2019 ◽  
Vol 5 (1) ◽  
pp. eaav1848 ◽  
Author(s):  
Xueying C. Li ◽  
David Peris ◽  
Chris Todd Hittinger ◽  
Elaine A. Sia ◽  
Justin C. Fay
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cold Tolerance ◽  
Yeast Species ◽  
Saccharomyces Uvarum ◽  
Phenotypic Differences ◽  
Protein Divergence ◽  
Thermal Growth ◽  
Genome Wide ◽  
A Genome ◽  
Moderate Effect

Genetic analysis of phenotypic differences between species is typically limited to interfertile species. Here, we conducted a genome-wide noncomplementation screen to identify genes that contribute to a major difference in thermal growth profile between two reproductively isolated yeast species,Saccharomyces cerevisiaeandSaccharomyces uvarum. The screen identified only a single nuclear-encoded gene with a moderate effect on heat tolerance, but, in contrast, revealed a large effect of mitochondrial DNA (mitotype) on both heat and cold tolerance. Recombinant mitotypes indicate that multiple genes contribute to thermal divergence, and we show that protein divergence inCOX1affects both heat and cold tolerance. Our results point to the yeast mitochondrial genome as an evolutionary hotspot for thermal divergence.

scholarly journals An inducible CRISPR interference library for genetic interrogation of Saccharomyces cerevisiae biology

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Amir Momen-Roknabadi ◽  
Panos Oikonomou ◽  
Maxwell Zegans ◽  
Saeed Tavazoie
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Transcriptional Repression ◽  
Nucleosome Occupancy ◽  
Design Parameters ◽  
Experimental Conditions ◽  
Crispr Interference ◽  
Cellular Processes ◽  
Genome Wide ◽  
Reliable Assessment ◽  
A Genome

AbstractGenome-scale CRISPR interference (CRISPRi) is widely utilized to study cellular processes in a variety of organisms. Despite the dominance of Saccharomyces cerevisiae as a model eukaryote, an inducible genome-wide CRISPRi library in yeast has not yet been presented. Here, we present a genome-wide, inducible CRISPRi library, based on spacer design rules optimized for S. cerevisiae. We have validated this library for genome-wide interrogation of gene function across a variety of applications, including accurate discovery of haploinsufficient genes and identification of enzymatic and regulatory genes involved in adenine and arginine biosynthesis. The comprehensive nature of the library also revealed refined spacer design parameters for transcriptional repression, including location, nucleosome occupancy and nucleotide features. CRISPRi screens using this library can identify genes and pathways with high precision and a low false discovery rate across a variety of experimental conditions, enabling rapid and reliable assessment of genetic function and interactions in S. cerevisiae.

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