The human gene ERCC-3 specifically corrects the defect in an early step of the DNA excision repair pathway of UV-sensitive rodent mutants of complementation group 3. The predicted 782 animo acid ERCC-3 protein harbors putative nucleotide, chromatin, and helix-turn-helix DNA binding domains and seven consecutive motifs conserved between two superfamilies of DNA and RNA helicases, strongly suggesting that it is a DNA repair helicase. ERCC-3-deficient rodent mutants phenotypically resemble the human repair syndrome xeroderma pigmentosum (XP). ERCC-3 specifically corrects the excision defect in one of the eight XP complementation groups, XP-B. The sole XP-B patient presents an exceptional conjunction of two rare repair disorders: XP and Cockayne's syndrome. This patient's DNA contains a C→A transversion in the splice acceptance sequence of the last intron of the only ERCC-3 allele that is detectable expressed, leading to a 4 bp insertion in the mRNA and an inactivating frameshift in the C-terminus of the protein. Because XP is associated with predisposition with skin cancer, ERCC-3 can be condidered a tumor-preventing gene.

*DNA Repair, 9007-49-2 (dna), Amino Acid Sequence, Base Sequence, Blotting, Northern, Blotting, Southern, Cloning, Molecular, Cockayne Syndrome/*enzymology/genetics, Comparative Study, DNA Helicases/*genetics, DNA/genetics, Dwarfism/*enzymology, EC 5.99.- (DNA Helicases), Genes, Structural, Human, Microinjections, Molecular Sequence Data, Polymerase Chain Reaction, RNA Splicing, Restriction Mapping, Support, Non-U.S. Gov't, Xeroderma Pigmentosum/*enzymology/genetics
dx.doi.org/10.1016/0092-8674(90)90122-U, hdl.handle.net/1765/3020
Cell
Erasmus MC: University Medical Center Rotterdam

Weeda, G, van Ham, R.C.A, Vermeulen, W, Bootsma, D, van der Eb, A.J, & Hoeijmakers, J.H.J. (1990). A presumed DNA helicase, encoded by the excision repair gene ERCC-3 is involved in the human repair disorders xeroderma pigmentosum and Cockayne's syndrome. Cell, 62(4), 777–791. doi:10.1016/0092-8674(90)90122-U