Hyperresistance to DNA damaging agents in yeast

Candida albicans is not inhibited by a number of drugs known to affect fungal cells. The basis for this resistance in most cases is unknown but has been attributed to the general impermeability of the fungal cell envelope. A gene (BENr) formerly shown to be responsible for the resistance of C. albicans to benomyl and methotrexate was shown in the present study to confer resistance to four other inhibitory compounds: cycloheximide, benztriazoles, 4-nitroquinoline-N-oxide, and sulfometuron methyl. Analysis of the protein database revealed an apparent similarity of the C. albicans gene to membrane protein genes encoding antibiotic resistance in prokaryotes and eukaryotes and a high degree of identity to a recently cloned gene encoding cycloheximide resistance in Candida maltosa. We propose that BENr encodes a protein that operates in a fashion similar, but not identical, to that described for other multiple-drug resistance proteins.

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“…Resistance to formaldehyde in S. cerevisiae is conferred by the SFA gene product (25,36). The mode of action of this gene is unknown.…”

Section: Resultsmentioning

confidence: 99%

Candida albicans gene encoding resistance to benomyl and methotrexate is a multidrug resistance gene

Ben-Yaacov

Knoller

Caldwell

et al. 1994

Antimicrob Agents Chemother

139

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“…Some vectors based on dominant marker genes for selection of transformed cells have been established in recent years, which mediate resistance against amino acid analogs (3,4), antibiotics (5,6) or copper ions (7). In 1986, we described yeast multi-copy formaldehyde (FA) hyperresistance as a selection marker (8). This hyperresistance phenotype is achieved by overexpression of the S. cerevisiae gene SFA, coding for a glu-tathione-dependent formaldehyde dehydrogenase (9).…”

Section: Introductionmentioning

confidence: 99%

Genetic engineering of baker's and wine yeasts using formaldehyde hyperresistance-mediating plasmids

Schmidt

Comer

Grey

et al. 1997

Braz J Med Biol Res

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Yeast multi-copy vectors carrying the formaldehyde-resistance marker gene SFA have proved to be a valuable tool for research on industrially used strains of Saccharomyces cerevisiae. The genetics of these strains is often poorly understood, and for various reasons it is not possible to simply subject these strains to protocols of genetic engineering that have been established for laboratory strains of S. cerevisiae. We tested our vectors and protocols using 10 randomly picked baker's and wine yeasts all of which could be transformed by a simple protocol with vectors conferring hyperresistance to formaldehyde. The application of formaldehyde as a selecting agent also offers the advantage of its biodegradation to CO 2 during fermentation, i.e., the selecting agent will be consumed and therefore its removal during down-stream processing is not necessary. Thus, this vector provides an expression system which is simple to apply and inexpensive to use.

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“…Multiple-copy SFA-containing yeast strains of Saccharomyces cerevisiae show five-to seven-fold higher formaldehyde (FA) resistance than the corresponding wild type (Ruhland et al, 1986;Mack et al, 1988). This hyper-resistance phenotype (HYR to FA) is caused by overexpression of the SFA-encoded protein with a molecular weight of 41 kDa that functions as a long-chain alcohol and GSH-dependent FA dehydrogenase .…”

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confidence: 99%

Vector YFRp1 allows transformant selection in Saccharomyces cerevisiae via resistance to formaldehyde

Wehner¹,

Brendel²

1993

Yeast

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Formaldehyde (FA), a chemical with low toxic potential, is used as sole selective agent for transformation in the yeast Saccharomyces cerevisiae. Neither stable auxotrophic markers in recipient cells nor defined synthetic media are needed when multicopy vector YFRp1, containing the yeast SFA gene, is employed for yeast transformation. The SFA gene gives stability to the vector and its yeast (and other) passenger genes when transformants are propagated in complex media supplemented with 3-5 mM-FA. Use of inexpensive FA and non-synthetic, undefined media will lower the cost of yeast transformant propagation considerably and thus make feasible large-volume industrial application of transformants containing YFRp1 derivatives.

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Hyperresistance to DNA damaging agents in yeast

Cited by 17 publications

References 17 publications

Candida albicans gene encoding resistance to benomyl and methotrexate is a multidrug resistance gene

Candida albicans gene encoding resistance to benomyl and methotrexate is a multidrug resistance gene

Genetic engineering of baker's and wine yeasts using formaldehyde hyperresistance-mediating plasmids

Vector YFRp1 allows transformant selection in Saccharomyces cerevisiae via resistance to formaldehyde

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