Base excision DNA repair (BER) is an important process used by all living organisms to remove nonbulky lesions from DNA. BER is usually initiated by DNA glycosylases that excise a damaged base leaving an apurinic/apyrimidinic (AP) site, and an AP endonuclease then cuts DNA at the AP site, and the repair is completed by correct nucleotide insertion, end processing, and nick ligation. It has emerged recently that the BER machinery, in addition to genome protection, is crucial for active epigenetic demethylation in the vertebrates. This pathway is initiated by TET dioxygenases that oxidize the regulatory 5-methylcytosine, and the oxidation products are treated as substrates for BER. T:G mismatch-specific thymine-DNA glycosylase (TDG) and AP endonuclease 1 (APE1) catalyze the first two steps in BER-dependent active demethylation. In addition to the well-structured catalytic domains, these enzymes possess long tails that are structurally uncharacterized but involved in multiple interactions and regulatory functions. In this review, we describe the known roles of the tails in TDG and APE1, discuss the importance of order and disorder in their structure, and consider the evolutionary aspects of these accessory protein regions. We also propose that the tails may be important for the enzymes' oligomerization on DNA, an aspect of their function that only recently gained attention.

中文翻译：

---

阅读活性去甲基化途径中的靶向 DNA 损伤：真核 AP 核酸内切酶和胸腺嘧啶 DNA 糖基化酶的辅助结构域的作用。

碱基切除 DNA 修复 (BER) 是所有生物体用于从 DNA 中去除非大块损伤的重要过程。BER 通常由 DNA 糖基化酶启动，该酶切除受损的碱基，留下脱嘌呤/脱嘧啶 (AP) 位点，然后 AP 核酸内切酶在 AP 位点切割 DNA，修复通过正确的核苷酸插入、末端加工和切口连接完成. 最近发现，除了基因组保护外，BER 机制对于脊椎动物的表观遗传去甲基化也至关重要。该途径由氧化调节性 5-甲基胞嘧啶的 TET 双加氧酶启动，氧化产物被视为 BER 的底物。T:G 错配特异性胸腺嘧啶 DNA 糖基化酶 (TDG) 和 AP 核酸内切酶 1 (APE1) 催化 BER 依赖性活性去甲基化的前两个步骤。除了结构良好的催化结构域外，这些酶还具有长尾，其结构未表征但参与多种相互作用和调节功能。在这篇综述中，我们描述了尾巴在 TDG 和 APE1 中的已知作用，讨论了它们结构中有序和无序的重要性，并考虑了这些辅助蛋白区域的进化方面。我们还提出，尾巴可能对酶在 DNA 上的寡聚化很重要，这是它们功能的一个方面，直到最近才受到关注。讨论其结构中有序和无序的重要性，并考虑这些辅助蛋白质区域的进化方面。我们还提出，尾巴可能对酶在 DNA 上的寡聚化很重要，这是它们功能的一个方面，直到最近才受到关注。讨论其结构中有序和无序的重要性，并考虑这些辅助蛋白质区域的进化方面。我们还提出，尾巴可能对酶在 DNA 上的寡聚化很重要，这是它们功能的一个方面，直到最近才受到关注。