Transcriptioncoupled

TranscriptionCoupled refers to cellular processes that are tightly linked to transcription and that respond to transcriptional status or transcription-associated damage. In molecular biology, the term is most often used in reference to transcription-coupled nucleotide excision repair (TC-NER), a subpathway that preferentially repairs DNA lesions on the transcribed strand of active genes. This coupling ensures rapid restoration of transcriptional fidelity in genes that are being actively expressed, helping to maintain genome stability.

In bacteria, transcription-coupled repair begins when RNA polymerase stalls at a DNA lesion. A dedicated factor, such as Mfd, recognizes the stalled complex, displaces or remodels RNA polymerase, and recruits the UvrAB repair machinery to the site. The lesion is then processed by nucleases and repaired, allowing transcription to resume.

In eukaryotes, TC-NER involves recognition of a stalled RNA polymerase II by factors such as CSB and CSA. These factors coordinate recruitment of the core repair machinery, including TFIIH, XPA, XPG, and XPF-ERCC1, and promote chromatin remodeling to grant repair access. After excision and resynthesis, transcription can restart. The process is coordinated with chromatin modifiers and histone remodeling factors to facilitate access in the transcribed region.

Biological significance centers on protecting actively expressed genes from mutagenesis and ensuring efficient recovery of transcription after damage. Defects in TC-NER, particularly in CSA or CSB, are linked to disorders such as Cockayne syndrome. The concept of transcription-coupled repair is distinguished from global genome repair, which operates independently of transcriptional activity.