Sandler S J, Clark A J
Department of Molecular and Cell Biology, University of California, Berkeley 94720.
Genetics. 1993 Nov;135(3):643-54. doi: 10.1093/genetics/135.3.643.
We showed that sufficient overexpression of the wild-type recF gene interfered with three normal cell functions: (1) UV induction of transcription from the LexA-protein-repressed sulA promoter, (2) UV resistance and (3) cell viability at 42 degrees. To show this, we altered a low-level overexpressing recF+ plasmid with a set of structurally neutral mutations that increased the rate of expression of recF. The resulting high-level overexpressing plasmid interfered with UV induction of the sulA promoter, as did the low-level overexpressing plasmid. It also reduced UV resistance more than its low level progenitor and decreased viability at 42 degrees, an effect not seen with the low-level plasmid. We used the high-level plasmid to test four recF structural mutations for residual activity. The structural alleles consisted of an insertion mutation, two single amino acid substitution mutations and a double amino acid substitution mutation. On the Escherichia coli chromosome the three substitution mutations acted similarly to a recF deletion in reducing UV resistance in a recB21 recC22 sbcB15 sbcC201 genetic background. By this test, therefore, all three appeared to be null alleles. Measurements of conjugational recombination revealed, however, that the three substitution mutations may have residual activity. On the high-level overexpressing plasmid all three substitution mutations definitely showed partial activity. By contrast, the insertion mutation on the high-level overexpressing plasmid showed no partial activity and can be considered a true null mutation. One of the substitutions, recF143, showed a property attributable to a leaky mutation. Another substitution, recF4101, may block selectively two of the three interference phenotypes, thus allowing us to infer a mechanism for them.
我们发现野生型recF基因的充分过表达会干扰三种正常细胞功能:(1)紫外线诱导LexA蛋白抑制的sulA启动子转录;(2)紫外线抗性;(3)42摄氏度下的细胞活力。为了证明这一点,我们用一组结构中性突变改变了一个低水平过表达recF+的质粒,这些突变提高了recF的表达速率。所得的高水平过表达质粒干扰了sulA启动子的紫外线诱导,低水平过表达质粒也是如此。它还比其低水平的亲本更能降低紫外线抗性,并降低42摄氏度下的活力,而低水平质粒则没有这种效果。我们用高水平质粒测试了四个recF结构突变的残余活性。结构等位基因包括一个插入突变、两个单氨基酸取代突变和一个双氨基酸取代突变。在大肠杆菌染色体上,在recB21 recC22 sbcB15 sbcC201遗传背景下,这三个取代突变在降低紫外线抗性方面的作用与recF缺失相似。因此,通过这个测试,这三个似乎都是无效等位基因。然而,接合重组的测量结果显示,这三个取代突变可能具有残余活性。在高水平过表达质粒上,这三个取代突变肯定表现出部分活性。相比之下,高水平过表达质粒上的插入突变没有表现出部分活性,可以被认为是一个真正的无效突变。其中一个取代突变recF143表现出可归因于渗漏突变的特性。另一个取代突变recF4101可能选择性地阻断三种干扰表型中的两种,从而使我们能够推断出它们的机制。