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Yeast gene YRR1 , which is required for resistance to 4‐nitroquinoline N ‐oxide, mediates transcriptional activation of the multidrug resistance transporter gene SNQ2
Author(s) -
Cui Zhifeng,
Shiraki Toshiyuki,
Hirata Dai,
Miyakawa Tokichi
Publication year - 1998
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1046/j.1365-2958.1998.01027.x
Subject(s) - biology , multiple drug resistance , yeast , gene , transporter , resistance (ecology) , genetics , atp binding cassette transporter , drug resistance , ecology
We have cloned and characterized a Saccharomyces cerevisiae gene YRR1 that is important for resistance to the mutagen 4‐nitroquinoline N ‐oxide (4‐NQO). The wild‐type YRR1 gene encodes a protein that contains a Zn(II) 2 Cys 6 ‐type zinc‐finger motif. Disruption of the YRR1 gene leads to hypersensitivity to 4‐NQO. A dominant mutation ( YRR1‐1 ) that confers strong resistance to 4‐NQO has been identified. Epistasis analysis demonstrated that 4‐NQO resistances mediated by the YRR1 and YRR1‐1 alleles require the presence of the SNQ2 gene that encodes a multidrug resistance ATP binding cassette superfamily protein responsible for 4‐NQO export. Northern blot analysis of SNQ2 mRNA levels indicated that Yrr1p is involved in basal and drug‐induced transcriptional activation of SNQ2 , whereas Pdr1p/Pdr3p transcription factors are mainly involved in basal SNQ2 expression. In the YRR1‐1 mutant, the level of SNQ2 mRNA is constitutively elevated. These results establish that Yrr1p is important for 4‐NQO resistance by mediating transcriptional activation of the SNQ2 gene in response to the stress imposed by 4‐NQO. The gain‐of‐function mutation of Yrr1‐1p was attributable to the duplication of a 12‐amino‐acid sequence generated near the carboxy terminus.