The transcription-coupled repair (TCR) pathway resolves transcription-blocking DNA lesions to maintain cellular function and prevent transcriptional arrest. Stalled RNA polymerase II (RNAPII) triggers repair mechanisms, including RNAPII ubiquitination, which recruit UVSSA and TFIIH. Defects in TCR-associated genes cause disorders like Cockayne syndrome, UV-sensitive syndrome, xeroderma pigmentosum, and recently defined AMeDS. TCR safeguards transcription, linking its failure to neurodegeneration and disease phenotypes.
Keywords: AMeDS (aplastic anemia; Cockayne syndrome (CS); DNA‐protein crosslinks (DPCs); RNA polymerase II (RNAPII); UV‐sensitive syndrome (UVSS); and dwarfism syndrome); mental retardation; nucleotide excision repair (NER); transcription‐coupled repair (TCR); trichothiodystrophy (TTD); xeroderma pigmentosum (XP).
© 2024 The Author(s). FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.