ANTIMUTAGENIC DNA POLYMERASES OF BACTERIOPHAGE T4
ANTIMUTAGENIC DNA POLYMERASES OF BACTERIOPHAGE T4
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DOI：
10.1101/sqb.1968.033.01.039
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发表时间：
1968-01-01
期刊：
影响因子：
--
通讯作者：
ALLEN, EF
中科院分区：
文献类型：
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作者：
DRAKE, JW;ALLEN, EF
其表型由突变率增加组成的突变，无论是在整个基因组中还是在一些更局部的区域内，已经在多种生物体中发现，包括原核生物和真核生物。然而，直到最近，人们才对这些系统中的不稳定机制有了明显的了解。 Treffers 突变子 mutT 在大肠杆菌中产生的突变已被证明是由高度特异性的颠倒途径 AT--CG 引起的（Yanofsky 等，1966；Cox 和 Yanofsky，1967）。鼠伤寒沙门氏菌中位于 purA 基因座附近的突变子会诱导各种碱基对取代，并可能产生诱变碱基类似物（Kirchner，1960；Kirchner 和 Rudden，1966）。Speyer（1965）观察到噬菌体 T4 基因 43 中的温度敏感（ts）损伤可能会产生强大的突变效应。对两个这样的突变体 tsL56 和 tsL88 的研究表明它们产生转换和颠换（Speyer 等，1966）。这些突变体引起了相当大的普遍兴趣，因为基因 43 的产物被鉴定为 DNA 合成装置的一个组成部分，即在单链模板存在下负责 5'-~3' 方向链传播的聚合酶（de Waard 等，1965；Warner 和 Barnes，1966；Goulian 等，1968）。突变修饰的 DNA 聚合酶产生的突变活性有时被视为该酶在碱基选择中发挥直接作用的证据（Speyer 等，1966）。这一建议受到了 Freese 和 Freese (1967) 的质疑，理由是突变子活性不会与化学诱变产生协同相互作用，这表明酶上不存在碱基结合位点：如果存在碱基结合位点，突变酶上的位点可能会表现出与野生型酶相比，拒绝异常碱基的能力下降。
Mutations whose phenotype consists of an increased mutation rate, either throughout the genome or within some more localized region, have been discovered in a wide variety of organisms, including both procaryotes and eucaryotes. Only very recently, however, has any appreciable understanding been gained concerning mechanisms of destabilization in any of these systems. The mutations produced in E. coli by the Treffers mutator mutT have been shown to result from a highly specific transversional pathway, AT--~ CG (Yanofsky et al., 1966; Cox and Yanofsky, 1967). A mutator in S. typhimurium which maps near the purA locus induces miscellaneous base pair substitutions, and may produce a nmtagenic base analog (Kirchner, 1960; Kirchner and Rudden, 1966).Speyer (1965) observed that temperature-sensitive (ts) lesions in gene 43 of bacteriophage T4 may produce powerful mutator effects. Studies of two such mutants, tsL56 and tsL88, suggested that they produce both transitions and transversions (Speyer et al., 1966). These mutants were of considerable general interest because of the identification of the product of gene 43 as a component in the apparatus of DNA synthesis, namely a polymerase responsible for chain propagation in the 5'-~ 3'direction in the presence of singlestranded template (de Waard et al., 1965; Warner and Barnes, 1966; Goulian et al., 1968). Mutator activity resulting from mutationally modified DNA polymerases has sometimes been taken as evidence for a direct role for the enzyme in base selection (Speyer et al., 1966). This suggestion has been challenged by Freese and Freese (1967) on the grounds that mutator activity does not interact synergistically with chemical mutagenesis, suggesting the absence of base binding sites on the enzyme: were they present, the sites on the mutant enzyme would presumably exhibit a decreased ability to reject unusual bases compared to the wild-type enzyme.