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Complementation of the oxidatively damaged DNA repair defect in Cockayne syndrome A and B cells by Escherichia coli formamidopyrimidine DNA glycosylase.

Abstract
Repair of the oxidized purine 8-oxo-7,8-dihydroguanine (8-oxoGua) is inefficient in cells belonging to the B complementation group of Cockayne syndrome (CS-B), a developmental and neurological disorder characterized by defective transcription-coupled repair. We show here that cells belonging to the A complementation group (CS-A) are also defective in repair of 8-oxoGua and we demonstrate that expression of the Escherichia coli formamidopyrimidine DNA glycosylase (FPG) completely corrects the repair deficiency in both CS-A and CS-B cells. Phenotypically, CS-A cells are normally sensitive to toxicity and micronuclei induced by the oxidizing agent potassium bromate. CS-B cells display sensitivity to elevated concentrations of potassium bromate but this is not compensated by FPG expression, suggesting toxicity of lesions that are not FPG substrates. The data indicate that 8-oxoGua is not a major toxic and clastogenic lesion in CS cells.
AuthorsMonica Ropolo, Paolo Degan, Mara Foresta, Mariarosaria D'Errico, Denise Lasigliè, Eugenia Dogliotti, Gianluigi Casartelli, Simonetta Zupo, Alessandro Poggi, Guido Frosina
JournalFree radical biology & medicine (Free Radic Biol Med) Vol. 42 Issue 12 Pg. 1807-17 (Jun 15 2007) ISSN: 0891-5849 [Print] United States
PMID17512460 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Bromates
  • Carcinogens
  • potassium bromate
  • DNA-Formamidopyrimidine Glycosylase
Topics
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Bromates (pharmacology)
  • Carcinogens (pharmacology)
  • Cell Survival (drug effects)
  • Cells, Cultured (drug effects)
  • Cockayne Syndrome (genetics)
  • Colony-Forming Units Assay
  • DNA Damage
  • DNA Repair
  • DNA-Formamidopyrimidine Glycosylase (genetics, metabolism)
  • Escherichia coli (enzymology)
  • Female
  • Fibroblasts (drug effects)
  • Genetic Complementation Test
  • Genetic Vectors
  • Humans
  • Kidney (metabolism, pathology)
  • Male
  • Micronucleus Tests
  • Transcription, Genetic
  • Urinary Bladder Neoplasms (metabolism, pathology)

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