Templated mutagenesis in bacteriophage T4 involving imperfect direct or indirect sequence repeats
Templated mutagenesis in bacteriophage T4 involving imperfect direct or indirect sequence repeats
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DOI：
10.1534/genetics.107.083444
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发表时间：
2008-02-01
期刊：
影响因子：
3.3
通讯作者：
Drake, John W.
中科院分区：
文献类型：
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作者：
Schultz, Gary E., Jr.;Drake, John W.
一些突变与潜在的序列供体相关，该供体由不完美的直接或反向重复序列组成。许多这样的突变是复杂的;也就是说，它们由多个紧密的序列变化组成。目前的模型认为，复制DNA分子的引物末端解离，与异位模板重新退火，短暂延伸，然后返回到同源模板，带来局部不同的序列;或者，发夹结构可能形成突变中间体时，处理错配修复。这个过程类似于复制修复，其中引物延伸被模板中的损伤阻断;在这种情况下，异位模板是另一个子链，结果是无错误地绕过损伤。我们之前表明，损害复制修复的突变可以增强模板突变。我们在这里表明，模板化突变的强度可以是精致的敏感，其本地序列，不完美的反向重复的供体和受体臂可以交换角色，双突变体携带两个等位基因，每个影响模板化诱变和复制修复，可以有意想不到的表型。我们还记录了一个实例，其中两个特定位点的突变率与远端序列变化一致，但以一种似乎与模板诱变无关的方式变化。
Some mutations arise in association with a potential sequence donor that consists of an imperfect direct or reverse repeat. Many such mutations are complex; that is, they consist of multiple close sequence changes. Current models posit that the primer terminus of a replicating DNA molecule dissociates, reanneals with an ectopic template, extends briefly, and then returns to the cognate template, bringing with it a locally different sequence; alternatively, a hairpin structure may form the mutational intermediate when processed by mismatch repair. This process resembles replication repair, in which primer extension is blocked by a lesion in the template; in this case, the ectopic template is the other daughter strand, and the result is error-free bypass of the lesion. We previously showed that mutations that impair replication repair can enhance templated mutagenesis. We show here that the intensity of templated mutation can be exquisitely sensitive to its local sequence, that the donor and recipient arms of an imperfect inverse repeat can exchange roles, and that double mutants carrying two alleles, each affecting both templated mutagenesis and replication repair, can have unexpected phenotypes. We also record an instance in which the mutation rates at two particular sites change concordantly with a distant sequence change, but in a manner that appears unrelated to templated mutagenesis.