title: Deficient global genome repair of UV-induced cyclobutane pyrimidine dimers in terminally differentiated myocytes and proliferating fibroblasts from the rat heart.
abstract: Nucleotide excision repair (NER) is the principal pathway for the removal of a wide range of DNA helix-distorting lesions. Two NER subpathways have been identified, i.e. global genome repair (GGR) and transcription-coupled repair (TCR). Little is known about the expression of NER pathways in differentiated cells. We assessed the repair of UV-induced cyclobutane pyrimidine dimers (CPD) and 6-4-photoproducts (6-4 PP) in terminally differentiated myocytes and proliferating fibroblasts isolated from the hearts of neonatal rats. Myocytes and fibroblasts were found to carry out efficient removal of 6-4 PP but display poor repair of CPD by GGR. Furthermore, both cell types were found to carry out TCR of CPD, thus mimicking the repair phenotype of established rodent cell lines. The inefficient repair of CPD at the genome overall level occurs in the absence of massive apoptosis, but goes along with an undetectable level of transcription of the p48 gene, known to be mutated in xeroderma pigmentosum group E (XP-E) patients and recently proposed to be essential for repair of CPD in nonexpressed DNA. Taken together, the results suggest that primary non-dividing cardiac myocytes and proliferating fibroblasts from rat heart selectively remove CPD from the transcribed strand of transcriptionally active genes. GGR of CPD is poor due to the absence of p48 expression.
authors.affiliation: Department of Toxicogenetics, Leiden University Medical Center, Wassenaarseweg 72, 2333 AL, Leiden, The Netherlands.
authors.forename: Caroline G C
authors.initials: CG
authors.lastname: van der Wees
authors.forename: Maaike P G
authors.initials: MP
authors.lastname: Vreeswijk
authors.forename: Marion
authors.initials: M
authors.lastname: Persoon
authors.forename: Arnoud
authors.initials: A
authors.lastname: van der Laarse
authors.forename: Albert A
authors.initials: AA
authors.lastname: van Zeeland
authors.forename: Leon H F
authors.initials: LH
authors.lastname: Mullenders
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D005347:Fibroblasts / Q000528:radiation effects; D016678:Genome; D006321:Heart / Q000528:radiation effects*; D008297:Male; D032342:Muscle Cells / Q000528:radiation effects; D011740:Pyrimidine Dimers / Q000235:genetics*; D012313:RNA / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D051381:Rats; D017208:Rats, Wistar; D014466:Ultraviolet Rays
chemical_list: D011740:Pyrimidine Dimers; D012313:RNA; D004247:DNA; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases