title: Deficient repair of the transcribed strand of active genes in Cockayne's syndrome cells.
abstract: Removal of ultraviolet light induced cyclobutane pyrimidine dimers (CPD) from active and inactive genes was analyzed in cells derived from patients suffering from the hereditary disease Cockayne's syndrome (CS) using strand specific probes. The results indicate that the defect in CS cells affects two levels of repair of lesions in active genes. Firstly, CS cells are deficient in selective repair of the transcribed strand of active genes. In these cells the rate and efficiency of repair of CPD are equal for the transcribed and the nontranscribed strand of the active ADA and DHFR genes. In normal cells on the other hand, the transcribed strand of these genes is repaired faster than the nontranscribed strand. However, the nontranscribed strand is still repaired more efficiently than the inactive 754 gene and the gene coding for coagulation factor IX. Secondly, the repair level of active genes in CS cells exceeds that of inactive loci but is slower than the nontranscribed strand of active genes in normal cells. Our results support the model that CS cells lack a factor which is involved in targeting repair enzymes specifically towards DNA damage located in (potentially) active DNA.
authors.affiliation: MGC-Department of Radiation Genetics and Chemical Mutagenesis, State University of Leiden, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: van Hoffen
authors.forename: A T
authors.initials: AT
authors.lastname: Natarajan
authors.forename: L V
authors.initials: LV
authors.lastname: Mayne
authors.forename: A A
authors.initials: AA
authors.lastname: van Zeeland
authors.forename: L H
authors.initials: LH
authors.lastname: Mullenders
authors.forename: J
authors.initials: J
authors.lastname: Venema
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics*; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D003057:Cockayne Syndrome / Q000235:genetics*; D004249:DNA Damage; D004260:DNA Repair; D005347:Fibroblasts; D006801:Humans; D011740:Pyrimidine Dimers; D013539:Simian virus 40; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D011740:Pyrimidine Dimers; D013762:Tetrahydrofolate Dehydrogenase; D000243:Adenosine Deaminase