Defective repair of 5-hydroxy-2'-deoxycytidine in Cockayne syndrome cells and its complementation by Escherichia coli formamidopyrimidine DNA glycosylase and endonuclease III.

Abstract

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.

• Authors: Mara Foresta, Monica Ropolo, Paolo Degan, Ilaria Pettinati, Yoke W Kow, Gianluca Damonte, Alessandro Poggi, Guido Frosina
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 48 Issue 5 Pg. 681-90 (Mar 01 2010) ISSN: 1873-4596 [Electronic] United States
• PMID: 20026203 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2009 Elsevier Inc. All rights reserved.

Chemical References

• Escherichia coli Proteins
• Deoxycytidine
• 5-hydroxy-2'-deoxycytidine
• Deoxyribonuclease (Pyrimidine Dimer)
• NTH protein, E coli
• DNA-Formamidopyrimidine Glycosylase

Topics

• Adolescent
• Aged, 80 and over
• Cell Line, Transformed
• Child, Preschool
• Chromatin Assembly and Disassembly (genetics)
• Cockayne Syndrome (genetics, metabolism, therapy)
• DNA Repair-Deficiency Disorders (genetics)
• DNA-Formamidopyrimidine Glycosylase (genetics, metabolism)
• Deoxycytidine (analogs & derivatives, metabolism)
• Deoxyribonuclease (Pyrimidine Dimer) (genetics, metabolism)
• Escherichia coli (enzymology)
• Escherichia coli Proteins (genetics, metabolism)
• Female
• Humans
• Male
• Transfection