title: The Streptomyces peucetius drrC gene encodes a UvrA-like protein involved in daunorubicin resistance and production.
abstract: The drrC gene, cloned from the daunorubicin (DNR)- and doxorubicin-producing strain of Streptomyces peucetius ATCC 29050, encodes a 764-amino-acid protein with a strong sequence similarity to the Escherichia coli and Micrococcus luteus UvrA proteins involved in excision repair of DNA. Expression of drrC was correlated with the timing of DNR production in the growth medium tested and was not dependent on the presence of DNR. Since introduction of drrC into Streptomyces lividans imparted a DNR resistance phenotype, this gene is believed to be a DNR resistance gene. The drrC gene could be disrupted in the non-DNR-producing S. peucetius dnrJ mutant but not in the wild-type strain, and the resulting dnrJ drrC double mutant was significantly more sensitive to DNR in efficiency-of-plating experiments. Expression of drrC in an E. coli uvrA strain conferred significant DNR resistance to this highly DNR-sensitive mutant. However, the DrrC protein did not complement the uvrA mutation to protect the mutant from the lethal effects of UV or mitomycin even though it enhanced the UV resistance of a uvrA+ strain. We speculate that the DrrC protein mediates a novel type of DNR resistance, possibly different from the mechanism of DNR resistance governed by the S. peucetius drrAB genes, which are believed to encode a DNR antiporter.
authors.affiliation: School of Pharmacy, University of Wisconsin, Madison, 53706, USA.
authors.forename: N
authors.initials: N
authors.lastname: Lomovskaya
authors.forename: S K
authors.initials: SK
authors.lastname: Hong
authors.forename: S U
authors.initials: SU
authors.lastname: Kim
authors.forename: L
authors.initials: L
authors.lastname: Fonstein
authors.forename: K
authors.initials: K
authors.lastname: Furuya
authors.forename: R C
authors.initials: RC
authors.lastname: Hutchinson
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000595:Amino Acid Sequence; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D004269:DNA, Bacterial / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000235:genetics*; D003630:Daunorubicin / Q000096:biosynthesis / Q000494:pharmacology*; D004351:Drug Resistance / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins; D005798:Genes, Bacterial; D008242:Lysogeny; D008969:Molecular Sequence Data; D013302:Streptomyces / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C068631:UvrA protein, E coli; D000251:Adenosine Triphosphatases; D003630:Daunorubicin