Base excision repair (BER) is a critical genome defense pathway that copes with a broad range of DNA lesions induced by endogenous or exogenous genotoxic agents. AP endonucleases in the BER pathway are responsible for removing the damaged bases and nicking the abasic sites. In plants, the BER pathway plays a critical role in the active demethylation of 5-methylcytosine (5mC) DNA modification. Here, we have determined the crystal structures of Arabidopsis AP endonuclease ARP in complex with the double-stranded DNA containing tetrahydrofuran (THF) that mimics the abasic site. We identified the critical residues in ARP for binding and removing the abasic site and the unique residues for interacting with the orphan base. Additionally, we investigated the differences among the three plant AP endonucleases and evaluated the general DNA repair capacity of ARP in a mammalian cell line. Our studies provide further mechanistic insights into the BER pathway in plants.

中文翻译：

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AP 核酸内切酶 AtARP 催化机制的结构见解


碱基切除修复 (BER) 是一种关键的基因组防御途径，可应对内源性或外源性基因毒剂引起的广泛 DNA 损伤。 BER 途径中的 AP 核酸内切酶负责去除受损碱基并在无碱基位点上产生切口。在植物中，BER 途径在 5-甲基胞嘧啶 (5mC) DNA 修饰的主动去甲基化中发挥着关键作用。在这里，我们确定了拟南芥 AP 核酸内切酶 ARP 与模拟无碱基位点的含有四氢呋喃 (THF) 的双链 DNA 复合物的晶体结构。我们鉴定了 ARP 中用于结合和去除脱碱基位点的关键残基以及用于与孤碱基相互作用的独特残基。此外，我们研究了三种植物 AP 核酸内切酶之间的差异，并评估了哺乳动物细胞系中 ARP 的一般 DNA 修复能力。我们的研究为植物中的 BER 途径提供了进一步的机制见解。