title: Less repair of pyrimidine dimers and single-strand breaks in genes by scid cells.
abstract: Severe combined immunodeficient (Scid) mice have a mutation in the catalytic subunit of the DNA binding protein kinase that is involved in repair of double-strand breaks in DNA. To determine if the protein also influences repair of single-strand breaks, we examined the ability of Scid cells to repair lesions introduced by ultraviolet light and gamma-ray irradiation. DNA repair was measured both in total genomic DNA and in specific genes from murine Scid and wildtype fibroblast cell lines. The removal of pyrimidine dimers and repair of strand breaks in genes was measured using quantitative Southern blot analyses. After ultraviolet irradiation, there was no significant difference in the repair of photoproducts in bulk DNA between Scid and wildtype cells, as measured by cellular survival and unscheduled DNA synthesis. However, deficient repair was evident in genes, where Scid cells had 25-50% less repair in the c-myc and dihydrofolate reductase genes. After gamma-irradiation, Scid fibroblasts had 20-35% less repair of DNA breaks in immunoglobulin kappa and heavy constant genes than wildtype cells. The data suggest that intact DNA-PK enzyme is needed for the efficient operation of cellular repair of pyrimidine dimers and single-strand breaks in genes, as well as in its established role in rejoining double-strand breaks.
authors.affiliation: Laboratory of Molecular Genetics, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, Maryland, 21224, USA.
authors.forename: R H
authors.initials: RH
authors.lastname: Alrefai
authors.forename: E J
authors.initials: EJ
authors.lastname: Beecham
authors.forename: V A
authors.initials: VA
authors.lastname: Bohr
authors.forename: P J
authors.initials: PJ
authors.lastname: Gearhart
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair / Q000235:genetics*; D005786:Gene Expression Regulation; D051379:Mice; D016513:Mice, SCID / Q000235:genetics*; D011725:Pyridines; D014466:Ultraviolet Rays
chemical_list: D011725:Pyridines; C023666:pyridine