Function
The function of the ERCC1 protein is predominantly in nucleotide excision repair (NER) of damaged DNA. NER is one of five separate DNA repair mechanisms that also include recombination repair, base excision repair, mismatch repair, and translesion synthesis.
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. ERCC1 has a role in homology-dependent gene targeting events. In telomere maintenance, XPF/ERCC1 degrades 3′ G-rich overhangs and may have other functions.
ERCC1 knockout mice are runted at birth and die from progressive hepatic insufficiency. Liver failure also occurs in XPF knockout mice, but not mice deficient in any other nucleotide excision repair protein.
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