Mutations in the herpes simplex virus DNA polymerase gene conferring hypersensitivity to aphidicolin.
Mutations in the herpes simplex virus DNA polymerase gene conferring hypersensitivity to aphidicolin.
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单纯疱疹病毒 DNA 聚合酶基因突变导致对 aphidicolin 过敏。
DOI：
10.1093/nar/11.15.5287
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发表时间：
1983
影响因子：
14.9
通讯作者：
Schaffer,PA
中科院分区：
文献类型：
--
作者：
Coen,DM;Furman,PA;Aschman,DP;Schaffer,PA
在噬菌斑减少试验中，检查了 14 种已知或可能含有单纯疱疹病毒 DNA 聚合酶基因突变的突变体对阿非迪霉素的敏感性。其中 11 人表现出对该药物某种程度的超敏反应；阿非迪霉素敏感性的改变与焦磷酸类似物膦酰乙酸的敏感性改变相关。这些突变体之一 PAA 5 特异的 DNA 聚合酶，将其活性抑制 50% 所需的阿菲迪霉素比其亲本菌株特异的聚合酶少大约七倍。导致 PAAr5 的阿菲迪霉素过敏表型的突变被定位到单纯疱疹病毒 DNA 聚合酶基因座的 0.8 kbp 区域。这些数据综合表明：1) 单纯疱疹病毒 DNA 聚合酶基因的突变可以改变对阿非迪霉素的敏感性，2) HSV 聚合酶在体内对阿非迪霉素敏感，3) 影响阿非迪霉素结合的氨基酸改变也可能影响焦磷酸盐交换释放位点，表明阿非迪霉素与该位点紧密结合。
Fourteen mutants known or likely to contain mutations in the herpes simplex virus DNA polymerase gene were examined for their sensitivity to aphidicolin in plaque reduction assays. Eleven of these exhibited some degree of hyper-sensitivity to the drug; altered aphidicolin-sensitivity correlated with altered sensitivity to the pyrophosphate analog, phosphonoacetic acid. The DNA polymerase specified by one of these mutants, PAA 5, required roughly seven-fold less aphidicolin to inhibit its activity by 50% than did polymerase specified by its parental strain. Mutations responsible for the aphidicolin-hypersensitivity phenotype of PAAr5 were mapped to an 0.8 kbp region in the herpes simplex virus DNA polymerase locus. These data taken together indicate that 1) mutations in the herpes simplex virus DNA polymerase gene can confer altered sensitivity to aphidicolin, 2) that the HSV polymerase is sensitive to aphidicolin in vivo, and 3) that amlno acid alterations which affect aphidicolin binding may affect the pyrophosphate exchange-release site as well, suggesting that aphidicolin binds in close proximity to this site.