转录障碍合成（TLS）DNA聚合酶最初被描述为参与绕过DNA损伤的容易发生错误的酶。然而，过去几十年的广泛研究揭示了这些酶在许多其他细胞过程中的关键作用，不仅包括损伤绕过，还包括DNA复制、DNA修复、表观遗传学、免疫信号以及病毒感染。本综述讨论了TLS聚合酶展示的广泛功能，包括其潜在的生化机制和相关的突变性。由于它们具有缓解复制压力的多任务能力，TLS聚合酶代表了癌细胞的细胞依赖性和关键脆弱性。因此，本综述还重点介绍了在癌症治疗中针对TLS聚合酶的当前和新兴策略。版权所有© 2023 Elsevier Inc. 保留所有权利。

Translesion synthesis (TLS) DNA polymerases were originally described as error-prone enzymes involved in the bypass of DNA lesions. However, extensive research over the past few decades has revealed that these enzymes play pivotal roles not only in lesion bypass, but also in a myriad of other cellular processes. Such processes include DNA replication, DNA repair, epigenetics, immune signaling, and even viral infection. This review discusses the wide range of functions exhibited by TLS polymerases, including their underlying biochemical mechanisms and associated mutagenicity. Given their multitasking ability to alleviate replication stress, TLS polymerases represent a cellular dependency and a critical vulnerability of cancer cells. Hence, this review also highlights current and emerging strategies for targeting TLS polymerases in cancer therapy.Copyright © 2023 Elsevier Inc. All rights reserved.