转录合成(TLS)DNA聚合酶最初被描述为涉及绕过DNA损伤的易错酶。然而,过去几十年的广泛研究表明,这些酶不仅在病变旁路中发挥关键作用,而且在无数其他细胞过程中。这些过程包括DNA复制,DNA修复,表观遗传学,免疫信号,甚至是病毒感染.这篇综述讨论了TLS聚合酶表现出的广泛功能,包括它们潜在的生化机制和相关的诱变性。考虑到它们减轻复制压力的多任务处理能力,TLS聚合酶代表癌细胞的细胞依赖性和关键脆弱性。因此,这篇综述还重点介绍了在癌症治疗中靶向TLS聚合酶的当前和新兴策略.
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.