Lomovskaya N, Hong S K, Kim S U, Fonstein L, Furuya K, Hutchinson R C
School of Pharmacy, University of Wisconsin, Madison, 53706, USA.
J Bacteriol. 1996 Jun;178(11):3238-45. doi: 10.1128/jb.178.11.3238-3245.1996.
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.
从产柔红霉素(DNR)和阿霉素的天蓝色链霉菌ATCC 29050菌株中克隆得到的drrC基因,编码一种764个氨基酸的蛋白质,该蛋白质与参与DNA切除修复的大肠杆菌和藤黄微球菌UvrA蛋白具有高度的序列相似性。在测试的生长培养基中,drrC的表达与DNR产生的时间相关,且不依赖于DNR的存在。由于将drrC导入变铅青链霉菌可赋予其DNR抗性表型,因此该基因被认为是一个DNR抗性基因。drrC基因可在不产DNR的天蓝色链霉菌dnrJ突变体中被破坏,但在野生型菌株中则不能,并且在平板接种效率实验中,所得的dnrJ drrC双突变体对DNR的敏感性显著增加。在大肠杆菌uvrA菌株中表达drrC可赋予该对DNR高度敏感的突变体显著的DNR抗性。然而,尽管DrrC蛋白增强了uvrA +菌株的紫外线抗性,但它并不能弥补uvrA突变以保护突变体免受紫外线或丝裂霉素的致死作用。我们推测,DrrC蛋白介导了一种新型的DNR抗性,可能不同于由天蓝色链霉菌drrAB基因所控制的DNR抗性机制,后者被认为编码一种DNR反向转运蛋白。