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

Mara Foresta, Monica Ropolo, Paolo Degan, Ilaria Pettinati, Yoke W. Kow, Gianluca Damonte, Alessandro Poggi, Guido Frosina

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)681-690
Number of pages10
JournalFree Radical Biology and Medicine
Volume48
Issue number5
DOIs
Publication statusPublished - Mar 1 2010

Keywords

  • Cockayne syndrome
  • DNA base excision repair
  • Free radicals
  • Neuropathology
  • Oxidatively damaged DNA

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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