ROLE OF GENE UVSX IN ERROR-PRONE REPAIR BY BACTERIOPHAGE T4

诱变剂增加了人类可遗传生育的负担 缺陷和癌症，可能还有心脏病。多数 大多数生物体中的诱变剂通过触发一个称为 易出错修复(EPR)。这种诱变剂的主要作用是 以阻碍DNA进程的方式破坏DNA 复制复合体。然后，EPR有助于在 模板化不佳(因此具有突变性)的方式。这个 噬菌体T4 uvsX基因在EPR中起核心作用 在重组中。它的产物是一种重组酶，一种可以 催化DNA分子之间的同源链交换。 这种蛋白在EPR中的具体作用仍然是个谜。 目前正在进行两项分析。首先，尽管有几个严重的 UvsX的突变只是半致死的，有迹象表明 即使对uvsX进行更剧烈的破坏，也可能是完全致命的。 因此，宿主可抑制突变将被引入到 该基因的几个早期密码子和由此产生的突变体 将在非抑制条件下进行生存能力测试。 在变种人无法存活的地方，死亡原因将是 通过分析DNA新陈代谢来寻找。第二，一种相关性 将在重组和突变之间寻找：在一个 交叉使用外部标记，新诱导的突变将 筛查局部增强的重组频率。

Mutagens contribute to the human burden of heritable birth defects and cancer and probably to heart disease as well. Most mutagens in most organisms act by triggering a process called error-prone repair (EPR). Such mutagens' primary action is to damage DNA in ways that block the progress of the DNA replication complex. EPR then facilitates damage bypass in a poorly templated (and therefore mutagenic) manner. The bacteriophage T4 uvsX gene plays a central role in EPR and also in recombination. Its product is a recombinase, a protein that catalyzes homologous strand exchange between DNA molecules. The specific role of this protein in EPR remains mysterious. Two analyses are underway. First, although several severe mutations of uvsX are only semilethal, there are hints that an even more drastic disruption of uvsX may be fully lethal. Therefore, host-suppressible mutations will be introduced into several of the early codons of the gene and the resulting mutants will be tested for viability under nonsuppressing conditions. Where the mutants are inviable, the cause of death will be sought by analysing DNA metabolism. Second, a correlation between recombination and mutagenesis will be sought: in a cross employing outside markers, newly induced mutations will be screened for locally enhanced frequencies of recombination.