Pierisin is a DNA-targeting ADP-ribosyltransferase found in cabbage white butterfly (Pieris rapae). Pierisin transfers an ADP-ribosyl moiety to the 2-amino group of the guanine residue in DNA, yielding N2-(ADP-ribos-1-yl)-2′-deoxyguanosine (N2-ADPR-dG). Generally, such chemically modified DNA is recognized as DNA damage and elicits cellular responses, including DNA repair pathways. In Escherichia coli and human cells, it has been experimentally demonstrated that N2-ADPR-dG is a substrate of the nucleotide excision repair system. Although DNA repair machineries can remove most lesions, some unrepaired damages frequently lead to mutagenesis through DNA replication. Replication past the damaged DNA template is called translesion DNA synthesis (TLS). In vitro primer extension experiments have shown that eukaryotic DNA polymerase κ is involved in TLS across N2-ADPR-dG. In many cases, TLS is error-prone and thus a mutagenic process. Indeed, the induction of G:C to T:A and G:C to C:G mutations by N2-ADPR-dG in the hypoxanthine phosphoribosyltransferase gene mutation assay with Chinese hamster cells and supF shuttle vector plasmids assay using human fibroblasts has been reported. This review provides a detailed overview of DNA repair, TLS and mutagenesis of N2-ADPR-dG induced by cabbage butterfly pierisin-1.
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机译:Pierisin 是一种靶向 DNA 的 ADP-核糖基转移酶,存在于卷心菜白蝶 (Pieris rapae) 中。Pierisin 将 ADP-核糖基部分转移到 DNA 中鸟嘌呤残基的 2-氨基上,产生 N2-(ADP-核糖-1-基)-2′-脱氧鸟苷 (N2-ADPR-dG)。通常,这种化学修饰的 DNA 被认为是 DNA 损伤并引发细胞反应,包括 DNA 修复途径。在大肠杆菌和人类细胞中,实验证明 N2-ADPR-dG 是核苷酸切除修复系统的底物。尽管 DNA 修复机制可以去除大多数损伤,但一些未修复的损伤经常导致通过 DNA 复制发生诱变。通过受损 DNA 模板的复制称为跨损伤 DNA 合成 (TLS)。体外引物延伸实验表明,真核 DNA 聚合酶 κ 参与 N2-ADPR-dG 的 TLS。在许多情况下,TLS 容易出错,因此是一个诱变过程。事实上,在用中国仓鼠细胞进行的次黄嘌磷酸核糖转移酶基因突变测定和使用人成纤维细胞的 supF 穿梭载体质粒测定中,N2-ADPR-dG 诱导 G:C 到 T:A 和 G:C 到 C:G 突变。本文详细介绍了卷心菜蝴蝶 pierisin-1 诱导的 N2-ADPR-dG 的 DNA 修复、TLS 和诱变。
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