Biochemical and photochemical mechanisms that produce different UV-induced mutation spectra.
Biochemical and photochemical mechanisms that produce different UV-induced mutation spectra.
复制标题
DOI：
10.1016/j.mrfmmm.2021.111762
复制
发表时间：
2021-07
期刊：
影响因子：
--
通讯作者：
Sanyal MR
中科院分区：
文献类型：
--
作者：
Sugiyama T;Keinard B;Best G;Sanyal MR
虽然紫外线诱导的突变已被广泛研究，但将紫外线诱导的DNA损伤转化为突变的精确机制仍然难以捉摸。一种充分研究的机制涉及DNA聚合酶（Pol）η和DNA聚合酶，其在跨嘧啶二聚体的跨损伤合成（TLS）期间产生C>T转换。我们以前提出了另一种生化机制，涉及多次紫外线照射，在黑暗中孵育之间。孵育促进嘧啶二聚体中胞嘧啶的自发脱氨基，并且随后的UV照射诱导将胞嘧啶转化为单体尿嘧啶残基的不依赖于光解酶的（直接）光逆转。在本文中，我们首先证明了自然阳光可以诱导这两个突变过程在体外。在300 nm处的单色UVB也再现了直接光反转。我们还证明了两种突变过程都需要在黑暗中照射后孵育，这表明胞嘧啶脱氨基作用是Pol η/λ依赖性和光逆转依赖性机制所必需的。另一种Y家族聚合酶Pol I在与Pol I I组合时也介导UV损伤模板上的诱变TLS。Pol 1依赖性突变在很大程度上不依赖于照射后孵育，表明胞嘧啶脱氨基对于该突变过程不是必需的。阳光照射也诱导C>A颠换，这可能是由鸟嘌呤残基的氧化引起的。最后，我们以与癌症突变特征相当的格式构建了体外突变谱。虽然Pol n依赖性和光逆转依赖性光谱都显示出与癌症标签（SBS 7a）的高度相似性，但Pol n依赖性突变光谱具有不同的T>A/C取代，其在另一种癌症标签（SBS 7 d）中发现。Pol 1依赖性T>A/C取代对T4嘧啶二聚体糖基化酶处理具有抗性，表明该突变过程不依赖于顺式-顺式嘧啶二聚体。讨论了紫外线诱变多种机制的最新模型。
Although UV-induced mutagenesis has been studied extensively, the precise mechanisms that convert UV-induced DNA damage into mutations remain elusive. One well-studied mechanism involves DNA polymerase (Pol) η and ζ, which produces C>T transitions during translesion synthesis (TLS) across pyrimidine dimers. We previously proposed another biochemical mechanism that involves multiple UV-irradiations with incubation in the dark in between. The incubation facilitates spontaneous deamination of cytosine in a pyrimidine dimer, and the subsequent UV irradiation induces photolyase-independent (direct) photoreversal that converts cytosine into monomeric uracil residue. In this paper, we first demonstrate that natural sunlight can induce both mutational processes in vitro. The direct photoreversal was also reproduced by monochromatic UVB at 300 nm. We also demonstrate that post-irradiation incubation in the dark is required for both mutational processes, suggesting that cytosine deamination is required for both the Pol η/ζ-dependent and the photoreversal-dependent mechanisms. Another Y-family polymerase Pol ι also mediated a mutagenic TLS on UV-damaged templates when combined with Pol ζ. The Pol ι-dependent mutations were largely independent of post-irradiation incubation, indicating that cytosine deamination was not essential for this mutational process. Sunlight-exposure also induced C>A transversions which were likely caused by oxidation of guanine residues. Finally, we constructed in vitro mutation spectra in a comparable format to cancer mutation signatures. While both Pol η-dependent and photoreversal-dependent spectra showed high similarities to a cancer signature (SBS7a), Pol ι-dependent mutation spectrum has distinct T>A/C substitutions, which are found in another cancer signature (SBS7d). The Pol ι-dependent T>A/C substitutions were resistant to T4 pyrimidine dimer glycosylase-treatment, suggesting that this mutational process is independent of cis-syn pyrimidine dimers. An updated model about multiple mechanisms of UV-induced mutagenesis is discussed.
登录
查看更多内容
影响因子：
5.6
作者：
JOHNS, HE;PEARSON, ML;LEBLANC, JC
通讯作者：
LEBLANC, JC
影响因子：
62.1
作者：
Genereux JC;Barton JK
通讯作者：
Barton JK
DOI：
10.1016/j.mrfmmm.2006.01.003
发表时间：
2006-07-25
影响因子：
2.3
作者：
Choi, Jun-Hyuk;Besaratinia, Ahmad;Pfeifer, Gerd P.
通讯作者：
Pfeifer, Gerd P.
DOI：
10.1073/pnas.0605247103
发表时间：
2006-11-28
影响因子：
11.1
作者：
Dumstorf, Chad A.;Clark, Alan B.;Kunkel, Thomas A.
通讯作者：
Kunkel, Thomas A.
影响因子：
8.4
作者：
de Gruijl, FR
通讯作者：
de Gruijl, FR