The Streptomyces peucetius drrC gene encodes a UvrA-like protein involved in daunorubicin resistance and production
The Streptomyces peucetius drrC gene encodes a UvrA-like protein involved in daunorubicin resistance and production
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DOI：
10.1128/jb.178.11.3238-3245.1996
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发表时间：
1996-06-01
影响因子：
3.2
通讯作者：
Hutchinson, R
中科院分区：
文献类型：
--
作者：
Lomovskaya, N;Hong, SK;Hutchinson, R
drrC基因克隆自peucestreptomyces peucetius ATCC 29050产柔红霉素（DNR）和产多柔红霉素的菌株，编码764个氨基酸的蛋白，与大肠杆菌和黄体微球菌的UvrA蛋白序列相似性强，参与DNA的切除修复，drrC的表达与所测试的生长培养基中DNR的产生时间相关，而不依赖于DNR的存在。由于将drrC引入到lividans链霉菌中赋予了DNR抗性表型，因此该基因被认为是DNR抗性基因。在不产生DNR的peucetius dnrJ突变株中，drrC基因可以被破坏，而在野生型菌株中则不被破坏，由此产生的dnrJ drrC双突变株对DNR的敏感性显著提高。在大肠杆菌uvrA菌株中表达drrC，对这种高度DNR敏感的突变体具有显著的DNR抗性。然而，DrrC蛋白并没有补充uvrA突变来保护突变体免受紫外线或丝裂霉素的致命影响，尽管它增强了uvrA（+）菌株的紫外线抗性。我们推测DrrC蛋白介导了一种新型的DNR抗性，可能不同于由S. peucetius drrAB基因控制的DNR抗性机制，该基因被认为编码DNR反转运蛋白。
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.