Amplification of the CUP1 gene is associated with evolution of copper tolerance in Saccharomyces cerevisiae

ABSTRACT In wine production, sulfites are widely used as antimicrobials and antioxidants, whereas copper is associated with fungicides and wine fining treatments. Therefore, wine yeasts are constantly exposed to these agents. Copper tolerance is related to the copy number of the CUP1 gene, encoding for a metallothionein involved in copper detoxification. In wine yeasts, sulfite resistance mainly depends on the presence of the translocation t(XVI;VIII) in the promoter region of the SSU1 gene. This gene encodes for a plasma membrane sulfite pump involved in sulfite metabolism and detoxification. Recently, a new translocation, t(XVI;VIII), was identified. In this work, 253 Saccharomyces cerevisiae strains, representing three vineyard populations from two different continents, were analyzed, along with 20 industrial starters. Copper and sulfites tolerance as well as distribution of CUP1 gene copy-number, t(XVI;VIII)and t(XVI;XV) of SSU1 gene were studied to evaluate the impact of these genomic variations on population phenotypes. The CUP1 gene copy-number was found to be highly variable, ranging from zero to 79 per strain. Moreover it differently impacted the copper tolerance in the populations of the two continents. The diffusion of t(XVI;VIII) and, for the first time, t(XVI;XV) was determined in the three vineyard populations. The correlation between the presence of the translocation and strain sulfite tolerance levels was significant only for the t(XVI;VIII).

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Copper tolerance in Saccharomyces cerevisiae

Letters in Applied Microbiology ◽

10.1111/j.1472-765x.1994.tb00860.x ◽

1994 ◽

Vol 18 (5) ◽

pp. 245-250 ◽

Cited By ~ 16

Author(s):

D. Brady ◽

D. Glaum ◽

J.R. Duncan

Keyword(s):

Saccharomyces Cerevisiae ◽

Copper Tolerance

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Identification and analysis of a Saccharomyces cerevisiae copper homeostasis gene encoding a homeodomain protein.

Molecular and Cellular Biology ◽

10.1128/mcb.14.12.7792 ◽

1994 ◽

Vol 14 (12) ◽

pp. 7792-7804 ◽

Cited By ~ 23

Author(s):

S A Knight ◽

K T Tamai ◽

D J Kosman ◽

D J Thiele

Keyword(s):

Saccharomyces Cerevisiae ◽

Carbon Source ◽

Sole Carbon Source ◽

Copper Resistance ◽

Yeast Cells ◽

Homeodomain Protein ◽

Mrna Levels ◽

Reading Frame ◽

Cup1 Gene ◽

Intracellular Copper

Yeast metallothionein, encoded by the CUP1 gene, and its copper-dependent transcriptional activator ACE1 play a key role in mediating copper resistance in Saccharomyces cerevisiae. Using an ethyl methanesulfonate mutant of a yeast strain in which CUP1 and ACE1 were deleted, we isolated a gene, designated CUP9, which permits yeast cells to grow at high concentrations of environmental copper, most notably when lactate is the sole carbon source. Disruption of CUP9, which is located on chromosome XVI, caused a loss of copper resistance in strains which possessed CUP1 and ACE1, as well as in the cup1 ace1 deletion strain. Measurement of intracellular copper levels of the wild-type and cup9-1 mutant demonstrated that total intracellular copper concentrations were unaffected by CUP9. CUP9 mRNA levels were, however, down regulated by copper when yeast cells were grown with glucose but not with lactate or glycerol-ethanol as the sole carbon source. This down regulation was independent of the copper metalloregulatory transcription factor ACE1. The DNA sequence of CUP9 predicts an open reading frame of 306 amino acids in which a 55-amino-acid sequence showed 47% identity with the homeobox domain of the human proto-oncogene PBX1, suggesting that CUP9 is a DNA-binding protein which regulates the expression of important copper homeostatic genes.

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Copper Tolerance and Biosorption of Saccharomyces cerevisiae during Alcoholic Fermentation

PLoS ONE ◽

10.1371/journal.pone.0128611 ◽

2015 ◽

Vol 10 (6) ◽

pp. e0128611 ◽

Cited By ~ 22

Author(s):

Xiang-yu Sun ◽

Yu Zhao ◽

Ling-ling Liu ◽

Bo Jia ◽

Fang Zhao ◽

...

Keyword(s):

Saccharomyces Cerevisiae ◽

Alcoholic Fermentation ◽

Copper Tolerance

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ACE1 regulates expression of the Saccharomyces cerevisiae metallothionein gene

Molecular and Cellular Biology ◽

10.1128/mcb.8.7.2745-2752.1988 ◽

1988 ◽

Vol 8 (7) ◽

pp. 2745-2752

Author(s):

D J Thiele

Keyword(s):

Saccharomyces Cerevisiae ◽

Metal Binding ◽

Gene Deletion ◽

Copper Resistance ◽

Low Molecular Weight ◽

Wild Type ◽

Positive Role ◽

Cup1 Gene ◽

Transcriptional Induction

Copper resistance in Saccharomyces cerevisiae is mediated, in large part, by the CUP1 locus, which encodes a low-molecular-weight, cysteine-rich metal-binding protein. Expression of the CUP1 gene is regulated at the level of transcriptional induction in response to high environmental copper levels. This report describes the isolation of a yeast mutant, ace1-1, which is defective in the activation of CUP1 expression upon exposure to exogenous copper. The ace1-1 mutation is recessive and lies in a genetic element that encodes a trans-acting CUP1 regulatory factor. The wild-type ACE1 gene was isolated by in vivo complementation and restores copper inducibility of CUP1 expression and copper resistance to the otherwise copper-sensitive ace1-1 mutant. Linkage analysis and gene deletion experiments verified that this gene represents the authentic ACE1 locus. ACE1 maps to the left arm of chromosome VII, 9 centimorgans centromere distal to lys5. The ACE1 gene appears to play a direct or indirect positive role in activation of CUP1 expression in response to elevated copper concentrations.

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ACE1 regulates expression of the Saccharomyces cerevisiae metallothionein gene.

Molecular and Cellular Biology ◽

10.1128/mcb.8.7.2745 ◽

1988 ◽

Vol 8 (7) ◽

pp. 2745-2752 ◽

Cited By ~ 198

Author(s):

D J Thiele

Keyword(s):

Saccharomyces Cerevisiae ◽

Metal Binding ◽

Gene Deletion ◽

Copper Resistance ◽

Low Molecular Weight ◽

Wild Type ◽

Positive Role ◽

Cup1 Gene ◽

Transcriptional Induction

Copper resistance in Saccharomyces cerevisiae is mediated, in large part, by the CUP1 locus, which encodes a low-molecular-weight, cysteine-rich metal-binding protein. Expression of the CUP1 gene is regulated at the level of transcriptional induction in response to high environmental copper levels. This report describes the isolation of a yeast mutant, ace1-1, which is defective in the activation of CUP1 expression upon exposure to exogenous copper. The ace1-1 mutation is recessive and lies in a genetic element that encodes a trans-acting CUP1 regulatory factor. The wild-type ACE1 gene was isolated by in vivo complementation and restores copper inducibility of CUP1 expression and copper resistance to the otherwise copper-sensitive ace1-1 mutant. Linkage analysis and gene deletion experiments verified that this gene represents the authentic ACE1 locus. ACE1 maps to the left arm of chromosome VII, 9 centimorgans centromere distal to lys5. The ACE1 gene appears to play a direct or indirect positive role in activation of CUP1 expression in response to elevated copper concentrations.

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Identification and analysis of a Saccharomyces cerevisiae copper homeostasis gene encoding a homeodomain protein

Molecular and Cellular Biology ◽

10.1128/mcb.14.12.7792-7804.1994 ◽

1994 ◽

Vol 14 (12) ◽

pp. 7792-7804

Author(s):

S A Knight ◽

K T Tamai ◽

D J Kosman ◽

D J Thiele

Keyword(s):

Saccharomyces Cerevisiae ◽

Carbon Source ◽

Sole Carbon Source ◽

Copper Resistance ◽

Yeast Cells ◽

Homeodomain Protein ◽

Mrna Levels ◽

Reading Frame ◽

Cup1 Gene ◽

Intracellular Copper

Yeast metallothionein, encoded by the CUP1 gene, and its copper-dependent transcriptional activator ACE1 play a key role in mediating copper resistance in Saccharomyces cerevisiae. Using an ethyl methanesulfonate mutant of a yeast strain in which CUP1 and ACE1 were deleted, we isolated a gene, designated CUP9, which permits yeast cells to grow at high concentrations of environmental copper, most notably when lactate is the sole carbon source. Disruption of CUP9, which is located on chromosome XVI, caused a loss of copper resistance in strains which possessed CUP1 and ACE1, as well as in the cup1 ace1 deletion strain. Measurement of intracellular copper levels of the wild-type and cup9-1 mutant demonstrated that total intracellular copper concentrations were unaffected by CUP9. CUP9 mRNA levels were, however, down regulated by copper when yeast cells were grown with glucose but not with lactate or glycerol-ethanol as the sole carbon source. This down regulation was independent of the copper metalloregulatory transcription factor ACE1. The DNA sequence of CUP9 predicts an open reading frame of 306 amino acids in which a 55-amino-acid sequence showed 47% identity with the homeobox domain of the human proto-oncogene PBX1, suggesting that CUP9 is a DNA-binding protein which regulates the expression of important copper homeostatic genes.

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