Leveraging Yeast Genetics to Model Evolutionarily Conserved Aspects of Human Disease

A special issue of Journal of Fungi (ISSN 2309-608X). This special issue belongs to the section "Fungal Genomics, Genetics and Molecular Biology".

Deadline for manuscript submissions: 30 November 2024 | Viewed by 3337

Special Issue Editor

Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Interests: yeast genetics; cystic fibrosis; aging; cellular quiescence; cancer; phenomic models of disease

Special Issue Information

Dear Colleagues,

Yeast genetics has led the way for biological exploration to ultimately understand many aspects of human disease. Examples include fundamental roles of the central dogma, the cell cycle, protein trafficking, mitochondrial function, epigenetics, and other processes underlying disease. The power of yeast as a genetic model derives primarily from its relatively simple, unicellular eukaryotic nature and several unique organismal characteristics, rendering it especially amenable to genetic analysis. Despite remarkable contributions to understanding the biology of human diseases, yeast continues to harbor potential that is relatively untapped for this purpose. For example, the evidence for genetic complexity underlying human biology and disease continues to increase, as does the utility of yeast genetics to address it. This Special Issue has a purposefully broad scope to help to accomplish the objective of illuminating the complex genetics of cellular processes contributing to human disease and how analyses in yeast can be leveraged to address it through integrative biology. We invite all colleagues with passion for this topic to summarize, demonstrate, and/or propose how yeast genetic analysis, including phenomic modeling, complements studies in human or other models to inform our understanding of disease and thus discover and advance genetic-based therapeutic strategies.

Dr. John L Hartman IV
Guest Editor

Manuscript Submission Information

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Keywords

  • yeast genetics
  • human disease
  • S. cerevisiae
  • S. pombe
  • phenomic modeling
  • integrative biology

Published Papers (2 papers)

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Research

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17 pages, 2939 KiB  
Article
Yeast Ribonucleotide Reductase Is a Direct Target of the Proteasome and Provides Hyper Resistance to the Carcinogen 4-NQO
by Daria S. Spasskaya, Kirill A. Kulagin, Evgenia N. Grineva, Pamila J. Osipova, Svetlana V. Poddubko, Julia A. Bubis, Elizaveta M. Kazakova, Tomiris T. Kusainova, Vladimir A. Gorshkov, Frank Kjeldsen, Vadim L. Karpov, Irina A. Tarasova and Dmitry S. Karpov
J. Fungi 2023, 9(3), 351; https://doi.org/10.3390/jof9030351 - 14 Mar 2023
Viewed by 1692
Abstract
Various external and internal factors damaging DNA constantly disrupt the stability of the genome. Cells use numerous dedicated DNA repair systems to detect damage and restore genomic integrity in a timely manner. Ribonucleotide reductase (RNR) is a key enzyme providing dNTPs for DNA [...] Read more.
Various external and internal factors damaging DNA constantly disrupt the stability of the genome. Cells use numerous dedicated DNA repair systems to detect damage and restore genomic integrity in a timely manner. Ribonucleotide reductase (RNR) is a key enzyme providing dNTPs for DNA repair. Molecular mechanisms of indirect regulation of yeast RNR activity are well understood, whereas little is known about its direct regulation. The study was aimed at elucidation of the proteasome-dependent mechanism of direct regulation of RNR subunits in Saccharomyces cerevisiae. Proteome analysis followed by Western blot, RT-PCR, and yeast plating analysis showed that upregulation of RNR by proteasome deregulation is associated with yeast hyper resistance to 4-nitroquinoline-1-oxide (4-NQO), a UV-mimetic DNA-damaging drug used in animal models to study oncogenesis. Inhibition of RNR or deletion of RNR regulatory proteins reverses the phenotype of yeast hyper resistance to 4-NQO. We have shown for the first time that the yeast Rnr1 subunit is a substrate of the proteasome, which suggests a common mechanism of RNR regulation in yeast and mammals. Full article
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Review

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20 pages, 2443 KiB  
Review
Exploring the Molecular Underpinnings of Cancer-Causing Oncohistone Mutants Using Yeast as a Model
by Xinran Zhang, Dorelle V. Fawwal, Jennifer M. Spangle, Anita H. Corbett and Celina Y. Jones
J. Fungi 2023, 9(12), 1187; https://doi.org/10.3390/jof9121187 - 11 Dec 2023
Viewed by 1137
Abstract
Understanding the molecular basis of cancer initiation and progression is critical in developing effective treatment strategies. Recently, mutations in genes encoding histone proteins that drive oncogenesis have been identified, converting these essential proteins into “oncohistones”. Understanding how oncohistone mutants, which are commonly single [...] Read more.
Understanding the molecular basis of cancer initiation and progression is critical in developing effective treatment strategies. Recently, mutations in genes encoding histone proteins that drive oncogenesis have been identified, converting these essential proteins into “oncohistones”. Understanding how oncohistone mutants, which are commonly single missense mutations, subvert the normal function of histones to drive oncogenesis requires defining the functional consequences of such changes. Histones genes are present in multiple copies in the human genome with 15 genes encoding histone H3 isoforms, the histone for which the majority of oncohistone variants have been analyzed thus far. With so many wildtype histone proteins being expressed simultaneously within the oncohistone, it can be difficult to decipher the precise mechanistic consequences of the mutant protein. In contrast to humans, budding and fission yeast contain only two or three histone H3 genes, respectively. Furthermore, yeast histones share ~90% sequence identity with human H3 protein. Its genetic simplicity and evolutionary conservation make yeast an excellent model for characterizing oncohistones. The power of genetic approaches can also be exploited in yeast models to define cellular signaling pathways that could serve as actionable therapeutic targets. In this review, we focus on the value of yeast models to serve as a discovery tool that can provide mechanistic insights and inform subsequent translational studies in humans. Full article
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