Complementation of the oxidatively damaged DNA repair defect in Cockayne syndrome A and B cells by Escherichia coli formamidopyrimidine DNA glycosylase.
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.
Ropolo
Monica
M
Experimental Oncology B Laboratory, Department of Translational Oncology, Istituto Nazionale Ricerca Cancro, Largo Rosanna Benzi n. 10, 16132 Genova, Italy.
Degan
Paolo
P
Foresta
Mara
M
D'Errico
Mariarosaria
M
Lasigliè
Denise
D
Dogliotti
Eugenia
E
Casartelli
Gianluigi
G
Zupo
Simonetta
S
Poggi
Alessandro
A
Frosina
Guido
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001959:Bromates / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D003057:Cockayne Syndrome / Q000235:genetics*; D003114:Colony-Forming Units Assay; D004249:DNA Damage; D004260:DNA Repair; D043382:DNA-Formamidopyrimidine Glycosylase / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D005816:Genetic Complementation Test; D005822:Genetic Vectors; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D015162:Micronucleus Tests; D014158:Transcription, Genetic; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology
D001959:Bromates; D002273:Carcinogens; C019536:potassium bromate; D043382:DNA-Formamidopyrimidine Glycosylase