The contribution of the S-phase checkpoint genes MEC1 and SGS1 to genome stability maintenance in Candida albicans

Melanie Legrand, Christine L. Chan, Peter A. Jauert, David T Kirkpatrick

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Genome rearrangements, a common feature of Candida albicans isolates, are often associated with the acquisition of antifungal drug resistance. In Saccharomyces cerevisiae, perturbations in the S-phase checkpoints result in the same sort of Gross Chromosomal Rearrangements (GCRs) observed in C. albicans. Several proteins are involved in the S. cerevisiae cell cycle checkpoints, including Mec1p, a protein kinase of the PIKK (phosphatidyl inositol 3-kinase-like kinase) family and the central player in the DNA damage checkpoint. Sgs1p, the ortholog of BLM, the Bloom's syndrome gene, is a RecQ-related DNA helicase; cells from BLM patients are characterized by an increase in genome instability. Yeast strains bearing deletions in MEC1 or SGS1 are viable (in contrast to the inviability seen with loss of MEC1 in S. cerevisiae) but the different deletion mutants have significantly different phenotypes. The mec1Δ/Δ colonies have a wild-type colony morphology, while the sgs1Δ/Δ mutants are slow-growing, producing wrinkled colonies with pseudohyphal-like cells. The mec1Δ/Δ mutants are only sensitive to ethylmethane sulfonate (EMS), methylmethane sulfonate (MMS), and hydroxyurea (HU) but the sgs1Δ/Δ mutants exhibit a high sensitivity to all DNA-damaging agents tested. In an assay for chromosome 1 integrity, the mec1Δ/Δ mutants exhibit an increase in genome instability; no change was observed in the sgs1Δ/Δ mutants. Finally, loss of MEC1 does not affect sensitivity to the antifungal drug fluconazole, while loss of SGS1 leads to an increased susceptibility to fluconazole. Neither deletion elevated the level of antifungal drug resistance acquisition.

Original languageEnglish (US)
Pages (from-to)823-830
Number of pages8
JournalFungal Genetics and Biology
Volume48
Issue number8
DOIs
StatePublished - Aug 1 2011

Fingerprint

S Phase Cell Cycle Checkpoints
Genomic Instability
Fungal Drug Resistance
Candida albicans
Saccharomyces cerevisiae
Fluconazole
Maintenance
Phosphotransferases
Bloom Syndrome
Ethyl Methanesulfonate
Genes
DNA Helicases
Methyl Methanesulfonate
Hydroxyurea
Chromosomes, Human, Pair 1
Phosphatidylinositols
Cell Cycle Checkpoints
Protein Kinases
DNA Damage
Yeasts

Keywords

  • Antifungal drug resistance
  • Cell cycle checkpoint
  • Genome stability
  • MEC1
  • SGS1

Cite this

The contribution of the S-phase checkpoint genes MEC1 and SGS1 to genome stability maintenance in Candida albicans. / Legrand, Melanie; Chan, Christine L.; Jauert, Peter A.; Kirkpatrick, David T.

In: Fungal Genetics and Biology, Vol. 48, No. 8, 01.08.2011, p. 823-830.

Research output: Contribution to journalArticle

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