The contribution of the S-phase checkpoint genes MEC1 and SGS1 to genome stability maintenance in Candida albicans.
The contribution of the S-phase checkpoint genes MEC1 and SGS1 to genome stability maintenance in Candida albicans.
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S期检查点基因MEC1和SGS1对白色念珠菌中基因组稳定性维持的贡献。
DOI：
10.1016/j.fgb.2011.04.005
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发表时间：
2011-08
影响因子：
3
通讯作者：
Kirkpatrick, David T.
中科院分区：
文献类型：
--
作者：
Legrand, Melanie;Chan, Christine L.;Jauert, Peter A.;Kirkpatrick, David T.
基因组重排是白念珠菌分离株的一个共同特征，通常与抗真菌药物耐药性的获得有关。在酿酒酵母中，S期检查点的扰动导致与在C.白色念珠菌。几种蛋白质参与了S.酿酒酵母细胞周期检查点，包括Mec 1 p，PIKK（磷脂酰肌醇3-激酶样激酶）家族的蛋白激酶和DNA损伤检查点中的中心参与者。Sgs 1 p是布鲁姆综合征基因BLM的直系同源物，是一种RecQ相关的DNA解旋酶;来自BLM患者的细胞的特征是基因组不稳定性增加。MEC 1或SGS 1缺失的酵母菌株是活的（与S.酿酒酵母），但不同的缺失突变体具有显著不同的表型。mec 1 Δ/Δ菌落具有野生型菌落形态，而sgs 1 Δ/Δ突变体生长缓慢，产生具有假菌丝样细胞的褶皱菌落。mec 1 Δ/Δ突变体仅对甲磺酸乙酯（EMS）、甲磺酸甲酯（MMS）和羟基脲（HU）敏感，但sgs 1 Δ/Δ突变体对所有测试的DNA损伤剂均表现出高敏感性。在1号染色体完整性试验中，mec 1 Δ/Δ突变体显示基因组不稳定性增加;在sgs 1 Δ/Δ突变体中未观察到变化。最后，MEC 1的缺失不会影响抗真菌药物氟康唑的敏感性，而SGS 1的缺失会导致对氟康唑的敏感性增加。两种缺失均未提高抗真菌药物耐药性的获得水平。
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.
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影响因子：
5.3
作者：
GANGLOFF, S;MCDONALD, JP;ROTHSTEIN, R
通讯作者：
ROTHSTEIN, R
影响因子：
3.6
作者：
Legrand, M;Lephart, P;Magee, BB
通讯作者：
Magee, BB
影响因子：
30.8
作者：
Gangloff, S;Soustelle, C;Fabre, F
通讯作者：
Fabre, F
DOI：
10.1083/jcb.200605080
发表时间：
2006-12-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
Enserink JM;Smolka MB;Zhou H;Kolodner RD
通讯作者：
Kolodner RD
影响因子：
56.9
作者：
Magee, BB;Magee, PT
通讯作者：
Magee, PT