5-hydroxy-2--deoxycytidine and Cockayne-Syndrome

Repair of the oxidized purine 8-oxo-7,8-dihydro-2'-deoxyguanosine is inefficient in cells belonging to both complementation groups A and B of Cockayne syndrome (CS), a developmental and neurological disorder characterized by defective transcription-coupled repair. We show here that both CS-A and CS-B cells are also defective in the repair of 5-hydroxy-2'-deoxycytidine (5-OHdC), an oxidized pyrimidine with cytotoxic and mutagenic properties. The defect in the repair of oxidatively damaged DNA in CS cells thus extends to oxidized pyrimidines, indicating a general flaw in the repair of oxidized lesions in this syndrome. The defect could not be reproduced in in vitro repair experiments on oligonucleotide substrates, suggesting a role for both CS-A and CS-B proteins in chromatin remodeling during 5-OHdC repair. Expression of Escherichia coli formamidopyrimidine DNA glycosylase (FPG) or endonuclease III complemented the 5-OHdC repair deficiency. Hence, the expression of a single enzyme, FPG from E. coli, stably corrects the delayed removal of both oxidized purines and oxidized pyrimidines in CS cells.

Topics: Adolescent; Aged, 80 and over; Cell Line, Transformed; Child, Preschool; Chromatin Assembly and Disassembly; Cockayne Syndrome; Deoxycytidine; Deoxyribonuclease (Pyrimidine Dimer); DNA Repair-Deficiency Disorders; DNA-Formamidopyrimidine Glycosylase; Escherichia coli; Escherichia coli Proteins; Female; Humans; Male; Transfection