title: Molecular and cellular analysis of the DNA repair defect in a patient in xeroderma pigmentosum complementation group D who has the clinical features of xeroderma pigmentosum and Cockayne syndrome.
abstract: Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are quite distinct genetic disorders that are associated with defects in excision repair of UV-induced DNA damage. A few patients have been described previously with the clinical features of both disorders. In this paper we describe an individual in this category who has unusual cellular responses to UV light. We show that his cultured fibroblasts and lymphocytes are extremely sensitive to irradiation with UV-C, despite a level of nucleotide excision repair that is 30%-40% that of normal cells. The deficiency is assigned to the XP-D complementation group, and we have identified two causative mutations in the XPD gene: a gly-->arg change at amino acid 675 in the allele inherited from the patient's mother and a -1 frameshift at amino acid 669 in the allele inherited from his father. These mutations are in the C-terminal 20% of the 760-amino-acid XPD protein, in a region where we have recently identified several mutations in patients with trichothiodystrophy.
authors: MRC Cell Mutation Unit, University of Sussex, Falmer, Brighton, United Kingdom.
authors: B C
authors: BC
authors: Broughton
authors: A F
authors: AF
authors: Thompson
authors: S A
authors: SA
authors: Harcourt
authors: W
authors: W
authors: Vermeulen
authors: J H
authors: JH
authors: Hoeijmakers
authors: E
authors: E
authors: Botta
authors: M
authors: M
authors: Stefanini
authors: M D
authors: MD
authors: King
authors: C A
authors: CA
authors: Weber
authors: J
authors: J
authors: Cole
mesh_terms: D002478:Cells, Cultured; D002675:Child, Preschool; D003057:Cockayne Syndrome / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage; D004265:DNA Helicases / Q000172:deficiency / Q000235:genetics*; D004260:DNA Repair; D004268:DNA-Binding Proteins; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D005816:Genetic Complementation Test; D006579:Heterozygote; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D017354:Point Mutation; D011506:Proteins / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics; D014157:Transcription Factors; D014466:Ultraviolet Rays / Q000009:adverse effects; D014983:Xeroderma Pigmentosum / Q000145:classification / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D051759:Xeroderma Pigmentosum Group D Protein
chemical_list: D004268:DNA-Binding Proteins; D011506:Proteins; D014157:Transcription Factors; D004265:DNA Helicases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human