title: Phenotypic Consequences of a Spontaneous Loss of Heterozygosity in a Common Laboratory Strain of Candida albicans.
abstract: By testing the susceptibility to DNA damaging agents of several Candida albicans mutant strains derived from the commonly used laboratory strain, CAI4, we uncovered sensitivity to methyl methanesulfonate (MMS) in CAI4 and its derivatives, but not in CAF2-1. This sensitivity is not a result of URA3 disruption because the phenotype was not restored after URA3 reintroduction. Rather, we found that homozygosis of a short region of chromosome 3R (Chr3R), which is naturally heterozygous in the MMS-resistant-related strains CAF4-2 and CAF2-1, confers MMS sensitivity and modulates growth polarization in response to MMS. Furthermore, induction of homozygosity in this region in CAF2-1 or CAF4-2 resulted in MMS sensitivity. We identified 11 genes by SNP/comparative genomic hybridization containing only the a alleles in all the MMS-sensitive strains. Four candidate genes, SNF5, POL1, orf19.5854.1, and MBP1, were analyzed by generating hemizygous configurations in CAF2-1 and CAF4-2 for each allele of all four genes. Only hemizygous MBP1a/mbp1b::SAT1-FLIP strains became MMS sensitive, indicating that MBP1a in the homo- or hemizygosis state was sufficient to account for the MMS-sensitive phenotype. In yeast, Mbp1 regulates G1/S genes involved in DNA repair. A second region of homozygosis on Chr2L increased MMS sensitivity in CAI4 (Chr3R homozygous) but not CAF4-2 (Chr3R heterozygous). This is the first example of sign epistasis in C. albicans.
authors.affiliation: Departamento de Ciencias Biomédicas, Área Microbiología, Facultad de Ciencias, Universidad de Extremadura, 06006 Badajoz, Spain.
authors.forename: Toni
authors.identifier: 0000-0002-9303-1628
authors.initials: T
authors.lastname: Ciudad
authors.affiliation: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota 55455.
authors.forename: Meleah
authors.initials: M
authors.lastname: Hickman
authors.affiliation: Departamento de Ciencias Biomédicas, Área Microbiología, Facultad de Ciencias, Universidad de Extremadura, 06006 Badajoz, Spain.
authors.forename: Alberto
authors.identifier: 0000-0002-9050-8339
authors.initials: A
authors.lastname: Bellido
authors.affiliation: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota 55455 Department of Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, Israel.
authors.forename: Judith
authors.identifier: 0000-0002-8577-0084
authors.initials: J
authors.lastname: Berman
authors.affiliation: Departamento de Ciencias Biomédicas, Área Microbiología, Facultad de Ciencias, Universidad de Extremadura, 06006 Badajoz, Spain glarriba@unex.es.
authors.forename: Germán
authors.identifier: 0000-0001-6262-233X
authors.initials: G
authors.lastname: Larriba
mesh_terms: D000483:Alleles; D000935:Antifungal Agents / Q000633:toxicity; D002176:Candida albicans / Q000187:drug effects / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D004843:Epistasis, Genetic; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D019656:Loss of Heterozygosity / Q000187:drug effects / Q000235:genetics*; D008741:Methyl Methanesulfonate / Q000633:toxicity; D020641:Polymorphism, Single Nucleotide
chemical_list: D000935:Antifungal Agents; D005656:Fungal Proteins; D008741:Methyl Methanesulfonate
keywords: Candida albicans; LOH; MBP1; MMS susceptibility; growth polarization