Roles of Saccharomyces cerevisiae DNA polymerases Polη and Polζ in response to irradiation by simulated sunlight
Roles of Saccharomyces cerevisiae DNA polymerases Polη and Polζ in response to irradiation by simulated sunlight
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DOI：
10.1093/nar/gkg489
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发表时间：
2003-08-01
影响因子：
14.9
通讯作者：
Sage, E
中科院分区：
文献类型：
--
作者：
Kozmin, SG;Pavlov, YI;Sage, E
阳光会导致DNA损伤，如果DNA聚合酶无法修复或复制不准确，就会产生突变，导致人类患皮肤癌。DNA聚合酶eta （Poleta）和聚合酶zeta （Polzeta）分别由RAD30A和REV3基因编码。先前的研究已经研究了这些聚合酶在单色短波长UVC辐射（254 nm）照射的人和酵母细胞中的TLS作用。然而，我们对细胞对太阳辐射的反应知之甚少，太阳辐射具有更高的混合波长（310-1100 nm），会产生不同光谱的DNA损伤，包括杜瓦光产物和氧化损伤。本文报道了模拟日光（SSL）和UVC辐射对酵母野生型、rad30Delta、rev3Delta和rev3Delta rad30Delta菌株的细胞毒性和诱变效应的比较。SSL的结果支持了先前对这两种聚合酶在光二聚体和（6-4）光产物的TLS中的作用的解释。他们进一步认为Poleta参与了含ssl依赖胞嘧啶的杜瓦光产物和8-氧鸟嘌呤的非诱变旁路，而Polzeta主要负责所有类型杜瓦光产物的诱变旁路。他们还认为，在没有Polzeta的情况下，Poleta可能通过绕过含有脱氨胞嘧啶的光二聚体而促进UVC和ssl诱导的诱变。
Sunlight causes lesions in DNA that if unrepaired and inaccurately replicated by DNA polymerases yield mutations that result in skin cancer in humans. Two enzymes involved in translesion synthesis (TLS) of UV-induced photolesions are DNA polymerase eta (Poleta) and polymerase zeta (Polzeta), encoded by the RAD30A and REV3 genes, respectively. Previous studies have investigated the TLS roles of these polymerases in human and yeast cells irradiated with monochromatic, short wavelength UVC radiation (254 nm). However, less is known about cellular responses to solar radiation, which is of higher and mixed wavelengths (310-1100 nm) and produces a different spectrum of DNA lesions, including Dewar photoproducts and oxidative lesions. Here we report on the comparative cytotoxic and mutagenic effects of simulated sunlight (SSL) and UVC radiation on yeast wild-type, rad30Delta, rev3Delta and rev3Delta rad30Delta strains. The results with SSL support several previous interpretations on the roles of these two polymerases in TLS of photodimers and (6-4) photoproducts derived from studies with UVC. They further suggest that Poleta participates in the non-mutagenic bypass of SSL-dependent cytosine-containing Dewar photoproducts and 8-oxoguanine, while Polzeta is mainly responsible for the mutagenic bypass of all types of Dewar photoproducts. They also suggest that in the absence of Polzeta, Poleta contributes to UVC- and SSL-induced mutagenesis, possibly by the bypass of photodimers containing deaminated cytosine.