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Stress combined with loss of the Candida albicans SUMO protease Ulp2 triggers selection of aneuploidy via a two-step process

A delicate balance between genome stability and instability ensures genome integrity while generating genetic diversity, a critical step for evolution. Indeed, while excessive genome instability is harmful, moderated genome instability can drive adaptation to novel environments by maximising genetic...

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Autores principales: Rizzo, Marzia, Soisangwan, Natthapon, Vega-Estevez, Samuel, Price, Robert Jordan, Uyl, Chloe, Iracane, Elise, Shaw, Matt, Soetaert, Jan, Selmecki, Anna, Buscaino, Alessia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9829183/
https://www.ncbi.nlm.nih.gov/pubmed/36574460
http://dx.doi.org/10.1371/journal.pgen.1010576
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author Rizzo, Marzia
Soisangwan, Natthapon
Vega-Estevez, Samuel
Price, Robert Jordan
Uyl, Chloe
Iracane, Elise
Shaw, Matt
Soetaert, Jan
Selmecki, Anna
Buscaino, Alessia
author_facet Rizzo, Marzia
Soisangwan, Natthapon
Vega-Estevez, Samuel
Price, Robert Jordan
Uyl, Chloe
Iracane, Elise
Shaw, Matt
Soetaert, Jan
Selmecki, Anna
Buscaino, Alessia
author_sort Rizzo, Marzia
collection PubMed
description A delicate balance between genome stability and instability ensures genome integrity while generating genetic diversity, a critical step for evolution. Indeed, while excessive genome instability is harmful, moderated genome instability can drive adaptation to novel environments by maximising genetic variation. Candida albicans, a human fungal pathogen that colonises different parts of the human body, adapts rapidly and frequently to different hostile host microenvironments. In this organism, the ability to generate large-scale genomic variation is a key adaptative mechanism triggering dangerous infections even in the presence of antifungal drugs. Understanding how fitter novel karyotypes are selected is key to determining how C. albicans and other microbial pathogens establish infections. Here, we identified the SUMO protease Ulp2 as a regulator of C. albicans genome integrity through genetic screening. Deletion of ULP2 leads to increased genome instability, enhanced genome variation and reduced fitness in the absence of additional stress. The combined stress caused by the lack of ULP2 and antifungal drug treatment leads to the selection of adaptive segmental aneuploidies that partially rescue the fitness defects of ulp2Δ/Δ cells. Short and long-read genomic sequencing demonstrates that these novel genotypes are selected via a two-step process leading to the formation of novel chromosomal fragments with breakpoints at microhomology regions and DNA repeats.
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spelling pubmed-98291832023-01-10 Stress combined with loss of the Candida albicans SUMO protease Ulp2 triggers selection of aneuploidy via a two-step process Rizzo, Marzia Soisangwan, Natthapon Vega-Estevez, Samuel Price, Robert Jordan Uyl, Chloe Iracane, Elise Shaw, Matt Soetaert, Jan Selmecki, Anna Buscaino, Alessia PLoS Genet Research Article A delicate balance between genome stability and instability ensures genome integrity while generating genetic diversity, a critical step for evolution. Indeed, while excessive genome instability is harmful, moderated genome instability can drive adaptation to novel environments by maximising genetic variation. Candida albicans, a human fungal pathogen that colonises different parts of the human body, adapts rapidly and frequently to different hostile host microenvironments. In this organism, the ability to generate large-scale genomic variation is a key adaptative mechanism triggering dangerous infections even in the presence of antifungal drugs. Understanding how fitter novel karyotypes are selected is key to determining how C. albicans and other microbial pathogens establish infections. Here, we identified the SUMO protease Ulp2 as a regulator of C. albicans genome integrity through genetic screening. Deletion of ULP2 leads to increased genome instability, enhanced genome variation and reduced fitness in the absence of additional stress. The combined stress caused by the lack of ULP2 and antifungal drug treatment leads to the selection of adaptive segmental aneuploidies that partially rescue the fitness defects of ulp2Δ/Δ cells. Short and long-read genomic sequencing demonstrates that these novel genotypes are selected via a two-step process leading to the formation of novel chromosomal fragments with breakpoints at microhomology regions and DNA repeats. Public Library of Science 2022-12-27 /pmc/articles/PMC9829183/ /pubmed/36574460 http://dx.doi.org/10.1371/journal.pgen.1010576 Text en © 2022 Rizzo et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Rizzo, Marzia
Soisangwan, Natthapon
Vega-Estevez, Samuel
Price, Robert Jordan
Uyl, Chloe
Iracane, Elise
Shaw, Matt
Soetaert, Jan
Selmecki, Anna
Buscaino, Alessia
Stress combined with loss of the Candida albicans SUMO protease Ulp2 triggers selection of aneuploidy via a two-step process
title Stress combined with loss of the Candida albicans SUMO protease Ulp2 triggers selection of aneuploidy via a two-step process
title_full Stress combined with loss of the Candida albicans SUMO protease Ulp2 triggers selection of aneuploidy via a two-step process
title_fullStr Stress combined with loss of the Candida albicans SUMO protease Ulp2 triggers selection of aneuploidy via a two-step process
title_full_unstemmed Stress combined with loss of the Candida albicans SUMO protease Ulp2 triggers selection of aneuploidy via a two-step process
title_short Stress combined with loss of the Candida albicans SUMO protease Ulp2 triggers selection of aneuploidy via a two-step process
title_sort stress combined with loss of the candida albicans sumo protease ulp2 triggers selection of aneuploidy via a two-step process
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9829183/
https://www.ncbi.nlm.nih.gov/pubmed/36574460
http://dx.doi.org/10.1371/journal.pgen.1010576
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