转录失灵DNA合成（TLS）是细胞用来克服DNA复制过程中遇到的损伤的一种DNA损伤容忍途径。在复制压力下，癌细胞对TLS蛋白的依赖性增加，以维持细胞生存和对化疗药物的耐药性。已经发现TLS蛋白参与多种DNA修复途径。TLS的一个重要新兴作用是在PrimPol遇到损伤后，主要在重新起动活动后用于填充单链DNA（ssDNA）缺口。相反，TLS通过抑制ssDNA缺口的积累，被认为是癌细胞回避化疗药物毒性的一种机制，特别是在BRCA缺陷细胞中。因此，TLS抑制正在成为DNA修复缺陷性肿瘤的潜在治疗方案。版权所有 © 2023 年爱思唯尔有限公司。保留所有权利。

Translesion DNA synthesis (TLS) is a DNA damage tolerance pathway utilized by cells to overcome lesions encountered throughout DNA replication. During replication stress, cancer cells show increased dependency on TLS proteins for cellular survival and chemoresistance. TLS proteins have been described to be involved in various DNA repair pathways. One of the major emerging roles of TLS is single-stranded DNA (ssDNA) gap-filling, primarily after the repriming activity of PrimPol upon encountering a lesion. Conversely, suppression of ssDNA gap accumulation by TLS is considered to represent a mechanism for cancer cells to evade the toxicity of chemotherapeutic agents, specifically in BRCA-deficient cells. Thus, TLS inhibition is emerging as a potential treatment regimen for DNA repair-deficient tumors.Copyright © 2023 Elsevier Ltd. All rights reserved.