A presumed DNA helicase encoded by ERCC-3 is involved in the human repair disorders xeroderma pigmentosum and Cockayne's syndrome.
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 amino 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 acceptor sequence of the last intron of the only ERCC-3 allele that is detectably 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 to skin cancer, ERCC-3 can be considered a tumor-preventing gene.
Weeda
G
G
Laboratory for Molecular Carcinogenesis, Sylvius Laboratory, Leiden, The Netherlands.
van Ham
R C
RC
Vermeulen
W
W
Bootsma
D
D
van der Eb
A J
AJ
Hoeijmakers
J H
JH
D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D003001:Cloning, Molecular; D003057:Cockayne Syndrome / Q000201:enzymology* / Q000235:genetics; D004247:DNA / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics*; D004260:DNA Repair; D004392:Dwarfism / Q000201:enzymology*; D005796:Genes; D006801:Humans; D008845:Microinjections; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D015183:Restriction Mapping; D014983:Xeroderma Pigmentosum / Q000201:enzymology* / Q000235:genetics
D004247:DNA; D004265:DNA Helicases