The ERCC1 polypeptide plays a crucial role in the nucleotide excision repair (NER) pathway, which is responsible for repairing damaged DNA. This polypeptide shares homology with the Saccharomyces cerevisiae RAD10 protein, involved in DNA repair and mitotic intra-chromosomal recombination. The NER mechanism involves making two cuts on either side of the DNA damage using two nucleases. In mammalian cells, XPG makes a cut at the 3' end of the DNA lesion, while the ERCC1-XPF complex makes the cut at the 5' end.
Excision Repair Cross-Complementing 1 (ERCC1) is a crucial protein involved in the nucleotide excision repair (NER) pathway, which is responsible for repairing a wide range of DNA lesions, including those induced by ultraviolet (UV) light and chemical mutagens. The human recombinant form of ERCC1 is a biotechnologically produced version of the naturally occurring protein, used extensively in research and therapeutic applications.
ERCC1 is a DNA repair protein encoded by the ERCC1 gene located on chromosome 19q13.32 . It forms a heterodimer with xeroderma pigmentosum group F (XPF) endonuclease, creating a complex that is essential for the NER pathway. This complex recognizes and excises damaged DNA strands, allowing for the subsequent repair and synthesis of new DNA .
The ERCC1-XPF complex is particularly important for the incision step of NER, where it makes dual incisions around the DNA lesion. This action is critical for removing bulky DNA adducts and cross-links, thereby maintaining genomic stability and preventing mutations that could lead to cancer .
ERCC1 has been extensively studied for its role in cancer biology and its potential as a biomarker for chemotherapy resistance. High levels of ERCC1 expression have been associated with resistance to platinum-based chemotherapies, such as cisplatin and carboplatin, which are commonly used to treat various cancers . This resistance occurs because the enhanced DNA repair capability conferred by ERCC1 allows cancer cells to survive and proliferate despite the DNA-damaging effects of these drugs .
In breast cancer, for example, ERCC1, along with other ERCC family genes, has been identified as a predictor of response to endocrine therapy and chemotherapy . The expression levels of ERCC1 can influence the effectiveness of treatment and overall prognosis, making it a valuable target for personalized cancer therapy .
The recombinant form of ERCC1 is produced using genetic engineering techniques, where the ERCC1 gene is inserted into a suitable expression system, such as bacteria or yeast, to produce the protein in large quantities. This recombinant protein is used in various research applications to study DNA repair mechanisms, screen for potential drug candidates, and develop therapeutic strategies for diseases associated with DNA repair deficiencies .
The clinical significance of ERCC1 extends beyond its role in cancer. Mutations or deficiencies in ERCC1 can lead to severe genetic disorders, such as xeroderma pigmentosum (XP) and Cockayne syndrome (CS), which are characterized by extreme sensitivity to UV light and a predisposition to skin cancers . Understanding the function and regulation of ERCC1 is therefore critical for developing treatments for these conditions.
In addition, ERCC1 is being investigated as a potential therapeutic target for enhancing the efficacy of existing cancer treatments. By modulating ERCC1 activity, it may be possible to sensitize cancer cells to chemotherapy and improve patient outcomes .