Factors that influence bidirectional long-tract homozygosis due to double-strand break repair in Candida albicans.
Alleles
Candida albicans
/ genetics
Chromosomes, Fungal
/ metabolism
DNA Breaks
DNA Breaks, Double-Stranded
DNA Repair
DNA Replication
Diploidy
Gene Rearrangement
Homozygote
Loss of Heterozygosity
Mutation
Recombination, Genetic
Saccharomyces cerevisiae
/ genetics
Saccharomyces cerevisiae Proteins
/ genetics
Candida albicans
bidirectional loss-of-heterozygosity
break induced replication
mitotic recombination
Journal
Genetics
ISSN: 1943-2631
Titre abrégé: Genetics
Pays: United States
ID NLM: 0374636
Informations de publication
Date de publication:
17 05 2021
17 05 2021
Historique:
received:
06
11
2020
accepted:
02
02
2021
pubmed:
12
3
2021
medline:
19
2
2022
entrez:
11
3
2021
Statut:
ppublish
Résumé
Genomic rearrangements have been associated with the acquisition of adaptive phenotypes, allowing organisms to efficiently generate new favorable genetic combinations. The diploid genome of Candida albicans is highly plastic, displaying numerous genomic rearrangements that are often the by-product of the repair of DNA breaks. For example, DNA double-strand breaks (DSB) repair using homologous-recombination pathways are a major source of loss-of-heterozygosity (LOH), observed ubiquitously in both clinical and laboratory strains of C. albicans. Mechanisms such as break-induced replication (BIR) or mitotic crossover (MCO) can result in long tracts of LOH, spanning hundreds of kilobases until the telomere. Analysis of I-SceI-induced BIR/MCO tracts in C. albicans revealed that the homozygosis tracts can ascend several kilobases toward the centromere, displaying homozygosis from the break site toward the centromere. We sought to investigate the molecular mechanisms that could contribute to this phenotype by characterizing a series of C. albicans DNA repair mutants, including pol32-/-, msh2-/-, mph1-/-, and mus81-/-. The impact of deleting these genes on genome stability revealed functional differences between Saccharomyces cerevisiae (a model DNA repair organism) and C. albicans. In addition, we demonstrated that ascending LOH tracts toward the centromere are associated with intrinsic features of BIR and potentially involve the mismatch repair pathway which acts upon natural heterozygous positions. Overall, this mechanistic approach to study LOH deepens our limited characterization of DNA repair pathways in C. albicans and brings forth the notion that centromere proximal alleles from DNA break sites are not guarded from undergoing LOH.
Identifiants
pubmed: 33705548
pii: 6168430
doi: 10.1093/genetics/iyab028
pmc: PMC8552485
pii:
doi:
Substances chimiques
Saccharomyces cerevisiae Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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