Environmental Molecular Toxicology, Department of Biological Chemistry, Graduate School of Science, Osaka Metropolitan University, 1-2 Gakuen-cho, Naka-ku, Sakai 599-8570, Japan.
Department of Environmental Health Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
Toxins (Basel). 2024 Jul 26;16(8):331. doi: 10.3390/toxins16080331.
Pierisin is a DNA-targeting ADP-ribosyltransferase found in cabbage white butterfly (). Pierisin transfers an ADP-ribosyl moiety to the 2-amino group of the guanine residue in DNA, yielding -(ADP-ribos-1-yl)-2'-deoxyguanosine (-ADPR-dG). Generally, such chemically modified DNA is recognized as DNA damage and elicits cellular responses, including DNA repair pathways. In and human cells, it has been experimentally demonstrated that -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 -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 -ADPR-dG in the hypoxanthine phosphoribosyltransferase gene mutation assay with Chinese hamster cells and shuttle vector plasmids assay using human fibroblasts has been reported. This review provides a detailed overview of DNA repair, TLS and mutagenesis of -ADPR-dG induced by cabbage butterfly pierisin-1.
Pierisin 是一种存在于白菜粉蝶（Pieris rapae）中的 DNA 靶向 ADP-ribosyltransferase。Pierisin 将 ADP-ribosyl 部分转移到 DNA 中鸟嘌呤残基的 2-氨基上，生成 -(ADP-ribos-1-yl)-2'-脱氧鸟苷 (-ADPR-dG)。通常，这种化学修饰的 DNA 被识别为 DNA 损伤，并引发细胞反应，包括 DNA 修复途径。在 和人类细胞中，实验证明 -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通过 DNA 复制导致突变。复制越过受损的 DNA 模板称为跨损伤 DNA 合成 (TLS)。体外引物延伸实验表明，真核 DNA 聚合酶 κ 参与了 -ADPR-dG 跨越的 TLS。在许多情况下，TLS 是易错的，因此是一个诱变过程。事实上，已报道 -ADPR-dG 在黄嘌呤磷酸核糖基转移酶基因突变检测中的中国仓鼠细胞和人成纤维细胞穿梭载体质粒检测中的 G:C 到 T:A 和 G:C 到 C:G 突变的诱导。这篇综述详细概述了白菜粉蝶 pierisin-1 诱导的 -ADPR-dG 的 DNA 修复、TLS 和诱变。
