Nucleotide excision repair in eukaryotes is initiated by either Global Genome NER(GG-NER) or Transcription Coupled NER(TC-NER) which involve distinct protein complexes, each recognizing damaged DNA. Thereafter, subsequent steps in GG-NER and TC-NER share a final common excision and repair pathway. Transcription factor II H (TFIIH) separates the abnormal strand from the normal strand. Xeroderma pigmentosum group G (XPG) cuts 3’ to the damaged DNA. Replication protein A (RPA) protects the normal strand. Xeroderma pigmentosum group A (XPA) isolates the damaged segment on the strand to be cut. ERCC1 and xeroderma pigmentosum group F (XPF) cut 5' to the damaged DNA. ERCC1 appears to have a crucial role in stabilizing and enhancing the functionality of the XPF endonuclease. The excised single-stranded DNA of approximately 30 nucleotides and attached NER proteins are removed. DNA polymerases and ligases fill in the gap using the normal strand as a template.
In mammals, the XPF/ERCC1 protein complex also removes nonhomologous 3′ tail ends in homologous recombination.... Read More