ERCC1  DNA excision repair protein ERCC-1 is a protein that in humans is encoded by the "ERCC1" gene. Together with ERCC4, ERCC1 forms the ERCC1-XPF enzyme complex that participates in DNA repair and DNA recombination. Many aspects of these two gene products are described together here because they are partners during DNA repair. The ERCC1-XPF nuclease is an essential activity in the pathway of DNA nucleotide excision repair (NER). The ERCC1-XPF nuclease also functions in pathways to repair double-strand breaks in DNA, and in the repair of “crosslink” damage that harmfully links the two DNA strands. Cells with disabling mutations in "ERCC1" are more sensitive than normal to particular DNA damaging agents, including ultraviolet (UV) radiation and to chemicals that cause crosslinking between DNA strands. Genetically engineered mice with disabling mutations in ERCC1 have defects in DNA repair, accompanied by metabolic stress-induced changes in physiology that result in premature aging. Complete deletion of ERCC1 is incompatible with viability of mice, and no human individuals have been found with complete (homozygous) deletion of ERCC1. Rare individuals in the human population harbor inherited mutations that impair the function of ERCC1. When the normal genes are absent, these mutations can lead to human syndromes, including Cockayne syndrome (CS) and COFS. "ERCC1" and "ERCC4" are the gene names assigned in mammalian genomes, including the human genome ("Homo sapiens"). Similar genes with similar functions are found in all eukaryotic organisms. The genomic DNA for "ERCC1" was the first human DNA repair gene to be isolated by molecular cloning. The original method was by transfer of fragments of the human genome to ultraviolet light (UV)-sensitive mutant cell lines derived from Chinese hamster ovary cells. Reflecting this cross-species genetic complementation method, the gene was called “Excision repair cross-complementing 1”. Multiple independent complementation groups of Chinese hamster ovary (CHO) cells were isolated, and this gene restored UV resistance to cells of complementation group 1. The human "ERCC1" gene encodes the ERCC1 protein of 297 amino acids with a molecular mass of about 32,500 daltons. Genes similar to "ERCC1" with equivalent functions (orthologs) are found in other eukaryotic genomes.