Transcription-coupled nucleotide excision repair complex (TC-NER complex) (TC-NER)

The Transcription-coupled nucleotide excision repair (TC-NER) complex is a specialized DNA repair assembly that prioritizes the removal of helix-distorting lesions from the transcribed strands of active genes (Marteijn et al., 2014, Nature Reviews Molecular Cell Biology). This process is triggered when RNA polymerase II (Pol II) encounters DNA damage, such as UV-induced photoproducts or bulky chemical adducts, and becomes physically stalled (Spivak, 2015, Archives of Toxicology). The stalled polymerase complex serves as a signal to recruit key TC-NER factors, including the Cockayne Syndrome proteins CSB (ERCC6) and CSA (ERCC8), which subsequently recruit the TFIIH complex and endonucleases to excise the damage (Vermeulen & Fousteri, 2013, Cold Spring Harbor Perspectives in Biology). In oncology, the TC-NER pathway is a critical determinant of resistance to platinum-based chemotherapies, as it efficiently removes the DNA cross-links these drugs induce (Damia & Broggini, 2014, Frontiers in Oncology). Conversely, genetic deficiencies in TC-NER components lead to severe disorders like Cockayne syndrome, characterized by growth failure, neurodegeneration, and premature aging (Gregersen & Svejstrup, 2012, Frontiers in Genetics). Therapeutic strategies often focus on inhibiting components of this complex, such as using spironolactone to degrade the XPB subunit of TFIIH, to sensitize cancer cells to DNA-damaging agents (Alekseev et al., 2014, Nature Communications).

Other names

Transcription-coupled repair complexTCR complexStalled RNA polymerase II repair complexCSB-CSA-UVSSA complex

Recognition and excision of DNA lesions on the transcribed strand of active genes, initiated by stalled RNA polymerase II.