A presumed DNA helicase encoded by ERCC-3 is involved in the human repair disorders xeroderma pigmentosum and Cockayne's syndrome
| Autor: | Reinier C.A. van Ham, Dirk Bootsma, Wim Vermeulen, Geert Weeda, Alex J. van der Eb, Jan H.J. Hoeijmakers |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
Xeroderma pigmentosum
DNA Repair Microinjections DNA repair RNA Splicing Molecular Sequence Data Restriction Mapping Dwarfism Polymerase Chain Reaction General Biochemistry Genetics and Molecular Biology Frameshift mutation chemistry.chemical_compound medicine Humans Amino Acid Sequence Cloning Molecular Cockayne Syndrome Gene Genetics Xeroderma Pigmentosum Base Sequence biology DNA Helicases Helicase DNA DNA-binding domain Blotting Northern medicine.disease Molecular biology Blotting Southern Genes chemistry biology.protein Nucleotide excision repair |
| Zdroj: | Cell. 62:777-791 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/0092-8674(90)90122-u |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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