跨模板合成（TLS）是一种维持基因组稳定并确保细胞在紧急情况下正常生长的DNA修复方式。作为一种易错性DNA聚合酶，Y家族DNA聚合酶主要执行TLS功能。先前的研究表明，肿瘤的发生与人类Y家族DNA聚合酶的过表达有关。并且，Y家族DNA聚合酶抑制剂的组合对癌症治疗具有潜力。本文报道了Y家族DNA聚合酶成员TTEDbh的功能和结构特征。我们确定TTEDbh是一种极端TLS聚合酶，能跨越氧化损伤位点，进一步确定了对DNA结合、合成、保真性和氧化损伤绕过至关重要的氨基酸和新颖结构。此外，我们还发现和分析了之前未注意到的具有重要功能的结构元素。这些研究为进一步阐明Y家族DNA聚合酶的分子机制提供了更多的实验基础。同时，这也有助于设计针对肿瘤的药物。版权所有 © 2023. 由Elsevier B.V.出版。

Translesion synthesis (TLS) is a kind of DNA repair that maintains the stability of the genome and ensures the normal growth of life in cells under emergencies. Y-family DNA polymerases, as a kind of error-prone DNA polymerase, mainly perform TLS. Previous studies have suggested that the occurrence of tumors is associated with the overexpression of human DNA polymerase of the Y family. And the combination of Y-family DNA polymerase inhibitors is promising for cancer therapy. Here we report the functional and structural characterization of a member of the Y-family DNA polymerases, TTEDbh. We determine TTEDbh is an extreme TLS polymerase that can cross oxidative damage sites, and further identify the amino acids and novel structures that are critical for DNA binding, synthesis, fidelity, and oxidative damage bypass. Moreover, previously unnoticed structural elements with important functions have been discovered and analyzed. These studies provide a more experimental basis for further elucidating the molecular mechanisms of DNA polymerase in the Y family. It could also shed light on the design of drugs to target tumors.Copyright © 2023. Published by Elsevier B.V.