Transcription elongation by RNA polymerase II (Pol II) is constantly challenged by numerous types of obstacles that lead to transcriptional pausing or stalling. These obstacles include DNA lesions, DNA epigenetic modifications, DNA binding proteins, and non-B form DNA structures. In particular, lesion-induced prolonged transcriptional blockage or stalling leads to genome instability, cellular dysfunction, and cell death. Transcription-coupled nucleotide excision repair (TC-NER) pathway is the first line of defense that detects and repairs these transcription-blocking DNA lesions. In this review, we will first summarize the recent research progress toward understanding the molecular basis of transcriptional pausing and stalling by different kinds of obstacles. We will then discuss new insights into Pol II-mediated lesion recognition and the roles of CSB in TC-NER.

RNA 聚合酶 II (Pol II) 的转录延长不断受到多种障碍的挑战，这些障碍会导致转录暂停或停滞。这些障碍包括 DNA 损伤、DNA 表观遗传修饰、DNA 结合蛋白和非 B 型 DNA 结构。特别是，病变诱导的长期转录阻断或停滞会导致基因组不稳定、细胞功能障碍和细胞死亡。转录偶联核苷酸切除修复 (TC-NER) 通路是检测和修复这些转录阻断 DNA 损伤的第一道防线。在这篇综述中，我们将首先总结最近在理解不同类型障碍引起的转录暂停和停滞的分子基础方面的研究进展。