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Genome Plasticity and DNA Repair in Candida albicans and Other...
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Genome Plasticity and DNA Repair in Candida albicans and Other Related Fungi

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: closed (31 March 2022) | Viewed by 10888

Special Issue Editors

Prof. Dr. Germán Larriba

E-Mail Website
Guest Editor
Department of Microbiology, Universidad de Extremadura, Badajoz, Spain
Interests: DNA-damaging agents; homologous recombination genes (RAD51, RAD52, RAD59, DLH1); loss-of-heterozygosity; aneuploidies; homologous recombination and DNA repair in Candida albicans
Dr. Toni Ciudad

E-Mail Website
Guest Editor
Department of Microbiology, Universidad de Extremadura, Badajoz, Spain
Interests: Candida albicans; genomic instability; mitotic recombination; DNA damage response; cell cycle; morphogenesis

Special Issue Information

Dear Colleagues

Pathogenic fungi cause mucosal and systemic infections that frequently threaten the life lives of immunocompromised patients. Without a functional immune system, antifungal therapy may sometimes be inefficient because of the genetic variability of pathogens. In fact, fungal pathogen resistance to currently used antifungal compounds is increasing all over the world and has become a serious threat to human health. This Special Issue of the Journal of Fungi will bring together experts with an extensive knowledge of the mechanisms that promote genome plasticity and the evolution of pathogenic fungi, with a special emphasis on Candida albicans.

Traditionally, Saccharomyces cerevisiae gave us a stable model for the molecular analysis of DNA repair. However, throughout the last twenty years this area has been extended to commensal and pathogenic fungi, including Ustilago maydis, Aspergillus fumigatus, Cryptococcus sp., and especially C. albicans, the most common human fungal pathogen. Comparative genomic and whole genome sequencing of clinical and natural isolates are powerful tools recently added to classical genetic approaches. With this methodology we can elaborate an exhaustive map of the fungal genome (repetitive sequences, telomeres, centromeres, translocations, indels, aneuploidies and heterozygosity) and analyse how these genomes evolve. Now, we are now closer than ever on our way to decode the secret of fungal pathogen´s evolution.

Prof. Dr. Germán Larriba
Dr. Toni Ciudad
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Fungi is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • fungal genetic instability
  • fungal microevolution
  • DNA repair
  • telomeres
  • mutation
  • chromosomes rearrangements
  • aneuploidy
  • loss of heterozygosity
  • DNA damage
  • mitotic recombination

Published Papers (4 papers)

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Research

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18 pages, 4555 KiB  
Article
Multiple Stochastic Parameters Influence Genome Dynamics in a Heterozygous Diploid Eukaryotic Model
by Timea Marton, Christophe d’Enfert and Melanie Legrand
J. Fungi 2022, 8(7), 650; https://doi.org/10.3390/jof8070650 - 21 Jun 2022
Cited by 1 | Viewed by 1393
Abstract
The heterozygous diploid genome of Candida albicans displays frequent genomic rearrangements, in particular loss-of-heterozygosity (LOH) events, which can be seen on all eight chromosomes and affect both laboratory and clinical strains. LOHs, which are often the consequence of DNA damage repair, can be [...] Read more.
The heterozygous diploid genome of Candida albicans displays frequent genomic rearrangements, in particular loss-of-heterozygosity (LOH) events, which can be seen on all eight chromosomes and affect both laboratory and clinical strains. LOHs, which are often the consequence of DNA damage repair, can be observed upon stresses reminiscent of the host environment, and result in homozygous regions of various sizes depending on the molecular mechanisms at their origins. Recent studies have shed light on the biological importance of these frequent and ubiquitous LOH events in C. albicans. In diploid Saccharomyces cerevisiae, LOH facilitates the passage of recessive beneficial mutations through Haldane’s sieve, allowing rapid evolutionary adaptation. This also appears to be true in C. albicans, where the full potential of an adaptive mutation is often only observed upon LOH, as illustrated in the case of antifungal resistance and niche adaptation. To understand the genome-wide dynamics of LOH events in C. albicans, we constructed a collection of 15 strains, each one carrying a LOH reporter system on a different chromosome arm. This system involves the insertion of two fluorescent marker genes in a neutral genomic region on both homologs, allowing spontaneous LOH events to be detected by monitoring the loss of one of the fluorescent markers using flow cytometry. Using this collection, we observed significant LOH frequency differences between genomic loci in standard laboratory growth conditions; however, we further demonstrated that comparable heterogeneity was also observed for a given genomic locus between independent strains. Additionally, upon exposure to stress, three outcomes could be observed in C. albicans, where individual strains displayed increases, decreases, or no effect of stress in terms of LOH frequency. Our results argue against a general stress response triggering overall genome instability. Indeed, we showed that the heterogeneity of LOH frequency in C. albicans is present at various levels, inter-strain, intra-strain, and inter-chromosomes, suggesting that LOH events may occur stochastically within a cell, though the genetic background potentially impacts genome stability in terms of LOH throughout the genome in both basal and stress conditions. This heterogeneity in terms of genome stability may serve as an important adaptive strategy for the predominantly clonal human opportunistic pathogen C. albicans, by quickly generating a wide spectrum of genetic variation combinations potentially permitting subsistence in a rapidly evolving environment. Full article
(This article belongs to the Special Issue Genome Plasticity and DNA Repair in Candida albicans and Other Related Fungi)
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17 pages, 2841 KiB  
Article
Abf1 Is an Essential Protein That Participates in Cell Cycle Progression and Subtelomeric Silencing in Candida glabrata
by Grecia Hernández-Hernández, Laura A. Vera-Salazar, Leonardo Castanedo, Eunice López-Fuentes, Guadalupe Gutiérrez-Escobedo, Alejandro De Las Peñas and Irene Castaño
J. Fungi 2021, 7(12), 1005; https://doi.org/10.3390/jof7121005 - 25 Nov 2021
Viewed by 1932
Abstract
Accurate DNA replication and segregation is key to reproduction and cell viability in all organisms. Autonomously replicating sequence-binding factor 1 (Abf1) is a multifunctional protein that has essential roles in replication, transcription, and regional silencing in the model yeast Saccharomyces cerevisiae. In [...] Read more.
Accurate DNA replication and segregation is key to reproduction and cell viability in all organisms. Autonomously replicating sequence-binding factor 1 (Abf1) is a multifunctional protein that has essential roles in replication, transcription, and regional silencing in the model yeast Saccharomyces cerevisiae. In the opportunistic pathogenic fungus Candida glabrata, which is closely related to S. cerevisiae, these processes are important for survival within the host, for example, the regulation of transcription of virulence-related genes like those involved in adherence. Here, we describe that CgABF1 is an essential gene required for cell viability and silencing near the telomeres, where many adhesin-encoding genes reside. CgAbf1 mediated subtelomeric silencing depends on the 43 C-terminal amino acids. We also found that abnormal expression, depletion, or overexpression of Abf1, results in defects in nuclear morphology, nuclear segregation, and transit through the cell cycle. In the absence of ABF1, cells are arrested in G2 but start cycling again after 9 h, coinciding with the loss of cell viability and the appearance of cells with higher DNA content. Overexpression of CgABF1 causes defects in nuclear segregation and cell cycle progression. We suggest that these effects could be due to the deregulation of DNA replication. Full article
(This article belongs to the Special Issue Genome Plasticity and DNA Repair in Candida albicans and Other Related Fungi)
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15 pages, 2290 KiB  
Article
Functional Roles of Homologous Recombination and Non-Homologous End Joining in DNA Damage Response and Microevolution in Cryptococcus neoformans
by Kwang-Woo Jung, Jong-Hyun Jung and Ha-Young Park
J. Fungi 2021, 7(7), 566; https://doi.org/10.3390/jof7070566 - 16 Jul 2021
Cited by 3 | Viewed by 2713
Abstract
DNA double-strand breaks (DSBs) are the most deleterious type of DNA lesions because they cause loss of genetic information if not properly repaired. In eukaryotes, homologous recombination (HR) and non-homologous end joining (NHEJ) are required for DSB repair. However, the relationship of HR [...] Read more.
DNA double-strand breaks (DSBs) are the most deleterious type of DNA lesions because they cause loss of genetic information if not properly repaired. In eukaryotes, homologous recombination (HR) and non-homologous end joining (NHEJ) are required for DSB repair. However, the relationship of HR and NHEJ in DNA damage stress is unknown in the radiation-resistant fungus Cryptococcus neoformans. In this study, we found that the expression levels of HR- and NHEJ-related genes were highly induced in a Rad53–Bdr1 pathway-dependent manner under genotoxic stress. Deletion of RAD51, which is one of the main components in the HR, resulted in growth under diverse types of DNA damage stress, whereas perturbations of KU70 and KU80, which belong to the NHEJ system, did not affect the genotoxic stresses except when bleomycin was used for treatment. Furthermore, deletion of both RAD51 and KU70/80 renders cells susceptible to oxidative stress. Notably, we found that deletion of RAD51 induced a hypermutator phenotype in the fluctuation assay. In contrast to the fluctuation assay, perturbation of KU70 or KU80 induced rapid microevolution similar to that induced by the deletion of RAD51. Collectively, Rad51-mediated HR and Ku70/Ku80-mediated NHEJ regulate the DNA damage response and maintain genome stability. Full article
(This article belongs to the Special Issue Genome Plasticity and DNA Repair in Candida albicans and Other Related Fungi)
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Review

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29 pages, 2645 KiB  
Review
Post-Translational Modifications of PCNA: Guiding for the Best DNA Damage Tolerance Choice
by Gemma Bellí, Neus Colomina, Laia Castells-Roca and Neus P. Lorite
J. Fungi 2022, 8(6), 621; https://doi.org/10.3390/jof8060621 - 10 Jun 2022
Cited by 6 | Viewed by 3980
Abstract
The sliding clamp PCNA is a multifunctional homotrimer mainly linked to DNA replication. During this process, cells must ensure an accurate and complete genome replication when constantly challenged by the presence of DNA lesions. Post-translational modifications of PCNA play a crucial role in [...] Read more.
The sliding clamp PCNA is a multifunctional homotrimer mainly linked to DNA replication. During this process, cells must ensure an accurate and complete genome replication when constantly challenged by the presence of DNA lesions. Post-translational modifications of PCNA play a crucial role in channeling DNA damage tolerance (DDT) and repair mechanisms to bypass unrepaired lesions and promote optimal fork replication restart. PCNA ubiquitination processes trigger the following two main DDT sub-pathways: Rad6/Rad18-dependent PCNA monoubiquitination and Ubc13-Mms2/Rad5-mediated PCNA polyubiquitination, promoting error-prone translation synthesis (TLS) or error-free template switch (TS) pathways, respectively. However, the fork protection mechanism leading to TS during fork reversal is still poorly understood. In contrast, PCNA sumoylation impedes the homologous recombination (HR)-mediated salvage recombination (SR) repair pathway. Focusing on Saccharomyces cerevisiae budding yeast, we summarized PCNA related-DDT and repair mechanisms that coordinately sustain genome stability and cell survival. In addition, we compared PCNA sequences from various fungal pathogens, considering recent advances in structural features. Importantly, the identification of PCNA epitopes may lead to potential fungal targets for antifungal drug development. Full article
(This article belongs to the Special Issue Genome Plasticity and DNA Repair in Candida albicans and Other Related Fungi)
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