Lesions in genes that result in RNA polymerase II (RNAPII) stalling or arrest are particularly toxic as they are a focal point of genome instability and potently block further transcription of the affected gene. Thus, cells have evolved the transcription-coupled nucleotide excision repair (TC-NER) pathway to identify damage-stalled RNAPIIs, so that the lesion can be rapidly repaired and transcription can continue. However, despite the identification of several factors required for TC-NER, how RNAPII is remodelled, modified, removed, or whether this is even necessary for repair remains enigmatic, and theories are intensely contested. Recent studies have further detailed the cellular response to UV-induced ubiquitylation and degradation of RNAPII and its consequences for transcription and repair. These advances make it pertinent to revisit the TC-NER process in general and with specific discussion of the fate of RNAPII stalled at DNA lesions.

导致 RNA 聚合酶 II (RNAPII) 停滞或停滞的基因损伤尤其有毒，因为它们是基因组不稳定的焦点，并有效阻止受影响基因的进一步转录。因此，细胞进化出了转录偶联核苷酸切除修复（TC-NER）途径来识别损伤停滞的RNAPII，从而使损伤得到快速修复，转录得以继续。然而，尽管确定了 TC-NER 所需的几个因素，但 RNAPII 是如何重塑、修改、去除的，或者这是否是修复所必需的，仍然是个谜，而且理论也存在激烈的争议。最近的研究进一步详细说明了细胞对 UV 诱导的 RNAPII 泛素化和降解的反应及其对转录和修复的影响。这些进展使得我们有必要重新审视一般的 TC-NER 过程，并具体讨论在 DNA 损伤处停滞的 RNAPII 的命运。