title: Repair of cyclobutane pyrimidine dimers or dimethylsulfate damage in DNA is identical in normal or telomerase-immortalized human skin fibroblasts.
abstract: The progression of a normal cell to senescence in vivo and in vitro is accompanied by a reduction in the length of the telomeres, the chromosome capping segments at the end of each linkage group. However, overexpression of the reverse transcriptase subunit (HTERT) of the ribonucleoprotein telomerase restores telomere length and delays cellular senescence. Although some data exist in the literature with respect to survival, no molecular data have shown that DNA repair in telomerase-immortalized cells is normal. Several telomerase-immortalized human skin fibroblast cell lines were constructed from a primary human fibroblast cell line. The primary line and the telomerase-immortalized cell lines were treated with either ultraviolet (UV) radiation or dimethylsulfate (DMS). UV radiation principally produces cyclobutane pyrimidine dimers that are repaired by nucleotide excision repair, whereas DMS introduces mainly N-methylpurines repaired by base excision repair. Here, we show that repair of both types of damage in the telomerase-immortalized human skin fibroblast cell lines is identical to repair observed in normal skin fibroblasts. Thus, telomerase expression and consequent immortalization of skin fibroblasts do not alter nucleotide or base excision repair in human cells.
authors.affiliation: Department of Biology, Beckman Research Institute, City of Hope National Medical Center 1450 East Duarte Road, Duarte, CA 91010, USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Bates
authors.forename: Ning Ye
authors.initials: NY
authors.lastname: Zhou
authors.forename: Laura E
authors.initials: LE
authors.lastname: Federico
authors.forename: Liqun
authors.initials: L
authors.lastname: Xia
authors.forename: Timothy R
authors.initials: TR
authors.lastname: O'Connor
mesh_terms: D000477:Alkylating Agents / Q000633:toxicity*; D002461:Cell Line, Transformed; D002470:Cell Survival; D002478:Cells, Cultured; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D011687:Purines / Q000378:metabolism; D011740:Pyrimidine Dimers / Q000378:metabolism*; D012867:Skin / Q000166:cytology; D013463:Sulfuric Acid Esters / Q000633:toxicity*; D019098:Telomerase / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D000477:Alkylating Agents; D004268:DNA-Binding Proteins; D011687:Purines; D011740:Pyrimidine Dimers; D013463:Sulfuric Acid Esters; D019098:Telomerase; C007482:dimethyl sulfate