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Requirement of DNA Polymerase η for Error-Free Bypass of UV-Induced CC and TC Photoproducts

机译:DNA聚合酶η对UV诱导的CC和TC光产品无错旁路的要求

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The yeast RAD30-encoded DNA polymerase η (Polη) bypasses a cis-syn thymine-thymine dimer efficiently and accurately. Human DNA polymerase η functions similarly in the bypass of this lesion, and mutations in human Polη result in the cancer prone syndrome, the variant form of xeroderma pigmentosum. UV light, however, also elicits the formation ofcis-syn cyclobutane dimers and (6-4) photoproducts at 5′-CC-3′ and 5′-TC-3′ sites, and in both yeast and human DNA, UV-induced mutations occur primarily by 3′ C to T transitions. Genetic studies presented here reveal a role for yeast Polη in the error-free bypass of cyclobutane dimers and (6-4) photoproducts formed at CC and TC sites. Thus, by preventing UV mutagenesis at a wide spectrum of dipyrimidine sites, Polη plays a pivotal role in minimizing the incidence of sunlight-induced skin cancers in humans.
机译:酵母 RAD30 编码的DNA聚合酶η(Polη)有效且准确地绕过了顺式-syn 胸腺嘧啶-胸腺嘧啶二聚体。人类DNA聚合酶η在绕过该病灶时的功能类似,而人类Polη中的突变会导致易患癌症的综合症,即干燥的皮肤干燥色素。但是,紫外线也会在5'-CC-3'和5'-TC-3'位以及在两个位点形成顺式-syn 环丁烷二聚体和(6-4)光产物的形成。酵母和人类DNA中,紫外线诱导的突变主要发生在3'C到T的转变。这里介绍的遗传研究揭示了酵母Polη在环丁烷二聚体和CC和TC位点形成的(6-4)光产物的无错旁路中的作用。因此,通过在二嘧啶位点的广谱范围内防止紫外线诱变,Polη在使人类中阳光诱发的皮肤癌的发生率最小化方面起着关键作用。

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