title: Gene-specific DNA repair in xeroderma pigmentosum complementation groups A, C, D, and F. Relation to cellular survival and clinical features.
abstract: We have examined the gene- and strand-specific DNA repair of UV-induced cyclobutane pyrimidine dimers in fibroblasts from normal individuals and from patients with the DNA repair-deficient disorder xeroderma pigmentosum (XP). Cells were studied from XP complementation groups A, C, D, and F. DNA repair was assessed in the essential, active gene, dihydrofolate reductase (DHFR), in the active c-myc protooncogene, and in the transcriptionally inactive delta-globin gene. In addition, repair was studied in the individual strands of the DHFR gene in normal and group C cells. In the two strains of group C cells, we find preferential DNA repair of the DHFR gene and a strand bias of the repair with more repair in the transcribed strand. This is in general accordance with previously published reports (Venema, J., van Hoffen, A., Natarajan, A.T., van Zeeland, A.A., and Mullenders, L.H.F. (1990) Nucleic Acids Res. 18, 443-448; Venema, J., van Hoffen, A., and Mullenders, L.H.F. (1991) Mol. Cell. Biol. 11, 4128-4134), but we now find that there is more repair in the nontranscribed strand and less in the transcribed strand than what has been observed previously. In XP group A and D strains, we find little or no gene-specific DNA repair. In cells from an individual in XP complementation group F, we find less repair of dimers in the active gene than what has been observed for the overall genome. We have also measured the colony-forming ability of the strains after treatment with UV and find that this measure of survival does not correlate with the level of gene-specific repair of dimers. Thus, XP group F represents a novel repair phenotype with little or no gene-specific repair of dimers, but with relatively high UV resistance. We also evaluate the XP patients' clinical features in relation to gene-specific repair of dimers.
authors.affiliation: Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: M K
authors.initials: MK
authors.lastname: Evans
authors.forename: J H
authors.initials: JH
authors.lastname: Robbins
authors.forename: M B
authors.initials: MB
authors.lastname: Ganges
authors.forename: R E
authors.initials: RE
authors.lastname: Tarone
authors.forename: R S
authors.initials: RS
authors.lastname: Nairn
authors.forename: V A
authors.initials: VA
authors.lastname: Bohr
mesh_terms: D000328:Adult; D000367:Age Factors; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D004260:DNA Repair / Q000235:genetics*; D005347:Fibroblasts; D016259:Genes, myc; D005816:Genetic Complementation Test; D005914:Globins / Q000235:genetics; D006801:Humans; D007223:Infant; D011740:Pyrimidine Dimers / Q000032:analysis; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics* / Q000503:physiopathology
chemical_list: D011740:Pyrimidine Dimers; D005914:Globins; D013762:Tetrahydrofolate Dehydrogenase