title: Glycosylases that excise modified DNA pyrimidines in young and senescent human WI-38 fibroblasts.
abstract: Cellular DNA is continuously subject to damages by both endogenous and exogenous oxidizing agents. Excision repair in human cells is initiated by DNA glycosylases which remove oxidized bases from DNA. 5-Hydroxymethyluracil-DNA glycosylase excises 5-hydroxymethyluracil from DNA. A different enzyme has glycosylic activity against many ring-saturated DNA pyrimidines. Levels of these enzymes were examined in WI-38 fibroblasts of different culture ages. All glycosylases were assayed by measurements of direct release of modified free bases from their respective DNA substrates. Levels of 5-hydroxymethyluracil-DNA glycosylase were reduced in aging cells. Specific activities of the glycosylase that releases ring-saturated pyrimidines and of uracil-DNA glycosylase were not substantially altered in senescent cells. Therefore, although aging cells might have reduced excision of DNA 5-hydroxymethyluracil, there is no overall age-dependent decrease of DNA glycosylase activities.
authors.affiliation: Department of Pathology, Temple University School of Medicine, Philadelphia, PA 19140.
authors.forename: T
authors.initials: T
authors.lastname: Ganguly
authors.forename: N J
authors.initials: NJ
authors.lastname: Duker
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000235:genetics*; D045647:DNA Glycosylases; D004260:DNA Repair / Q000502:physiology*; D004261:DNA Replication / Q000502:physiology; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D009699:N-Glycosyl Hydrolases / Q000378:metabolism*; D010432:Pentoxyl / Q000031:analogs & derivatives / Q000378:metabolism; D051981:Uracil-DNA Glycosidase
chemical_list: C008055:5-hydroxymethyluracil; D010432:Pentoxyl; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D051981:Uracil-DNA Glycosidase