TY - JOUR
T1 - A presumed DNA helicase encoded by ERCC-3 is involved in the human repair disorders xeroderma pigmentosum and Cockayne's syndrome
AU - Weeda, Geert
AU - van Ham, Reinier C.A.
AU - Vermeulen, Wim
AU - Bootsma, Dirk
AU - van der Eb, Alex J.
AU - Hoeijmakers, Jan H.J.
N1 - Funding Information:
We are grateful to Dr. T Berkvens, M. Koken, and Dr. K. Kraemer for help ful discussion, Dr. H. van Ormondt for critically reading this manuscript, 6. Klein (Leiden) for providing several immortalized XP cell lines, and Dr. G. Grosveld (Rotterdam) for donating the K562 cDNA library. We are indebted to Dr. H. Vrieling (Leiden) for helpful discussions and for help in the initial PCR experiments, M. Kuit is acknowledged for photography. This work was supported by the Netherlands Organization for Advancement of Pure Research (NWO) through the Foundation of Medical Scientific Research (contract no. 900~501-091) and by EURATOM (contract no BJ6-141-NL).
PY - 1990/8/24
Y1 - 1990/8/24
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/0025158110
U2 - 10.1016/0092-8674(90)90122-U
DO - 10.1016/0092-8674(90)90122-U
M3 - Article
C2 - 2167179
AN - SCOPUS:0025158110
SN - 0092-8674
VL - 62
SP - 777
EP - 791
JO - Cell
JF - Cell
IS - 4
ER -