21511048
not annotated - annotated - LINNAEUS only
The contribution of the S-phase checkpoint genes MEC1 and SGS1 to genome stability maintenance in Candida albicans.
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 mec1Delta/Delta colonies have a wild-type colony morphology, while the sgs1Delta/Delta mutants are slow-growing, producing wrinkled colonies with pseudohyphal-like cells. The mec1Delta/Delta mutants are only sensitive to ethylmethane sulfonate (EMS), methylmethane sulfonate (MMS), and hydroxyurea (HU) but the sgs1Delta/Delta mutants exhibit a high sensitivity to all DNA-damaging agents tested. In an assay for chromosome 1 integrity, the mec1Delta/Delta mutants exhibit an increase in genome instability; no change was observed in the sgs1Delta/Delta 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.
Ann file
T1 Species 98 114 Candida albicans
N1 Reference T1 Taxonomy:5476
T2 Species 161 177 Candida albicans
N2 Reference T2 Taxonomy:5476
T3 Species 264 288 Saccharomyces cerevisiae
N3 Reference T3 Taxonomy:4932
T4 Species 410 421 C. albicans
N4 Reference T4 Taxonomy:5476
T5 Species 460 473 S. cerevisiae
N5 Reference T5 Taxonomy:4932
T6 Out-of-scope 816 821 Yeast
T7 Species 933 946 S. cerevisiae
N7 Reference T7 Taxonomy:4932
N6 Reference T6 Taxonomy:147537 Saccharomycotina