ISOLATION OF 3 CONTIGUOUS GENES, ACR1, ACR2 AND ACR3, INVOLVED IN RESISTANCE TO ARSENIC COMPOUNDS IN THE YEAST SACCHAROMYCES-CEREVISIAE

A 4.2 kb region from Saccharomyces cerevisiae chromosome XVI was isola ted as a yeast fragment conferring resistance to 7 mM-sodium arsenite (NaAsO2), when put on a multicopy plasmid. Homology searches revealed a cluster of three new open reading frames named ACR1, ACR2 and ACR3. The hypothetical projuct of the ACR1 gene is similar to the transcript ional regulatory proteins, encoded by YAP1, and YAP2 genes from S. cer evisiae. Disruption of the ACR1 gene conduces to an arsenite and arsen ate hypersensitivity phenotype. The ACR2 gene is indispensable for ars enate but not for arsenite resistance. The hypothetical product of the ACR3 gene shows high similarity to the hypothetical membrane protein encoded by Bacillus subtilis ORF1 of the skin element and weak similar ity to the ArsB membrane protein of the Staphylococcus aureus arsenica l-resistance operon. Overexpression of the ACR3 gene confers an arseni te- but not an arsenate-resistance phenotype. The presence of ACR3 tog ether with ACR2 on a multicopy plasmid expands the resistance phenotyp e into arsenate. These findings suggest that all three novel genes: AC R1, ACR2 and ACR3 are involved in the arsenical-resistance phenomenon in S. cerevisiae. (C) 1997 by John Wiley & Sons, Ltd.