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PMID: 10890888 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Transcription coupled repair of 8-oxoguanine in murine cells: the ogg1 protein is required for repair in nontranscribed sequences but not in transcribed sequences.

Le Page F, Klungland A, Barnes DE, Sarasin A, Boiteux S

Abstract

To assess the role of the Ogg1 DNA glycosylase in the transcription-coupled repair (TCR) of the mutagenic lesion, 7, 8-dihydro-8oxoguanine (8-OxoG), we have investigated the removal of this lesion in wild-type and ogg1(-/-) null mouse embryo fibroblast (MEF) cell lines. We used nonreplicating plasmids containing a single 8-OxoG.C base pair in a different assay that allowed us to study the removal of 8-OxoG located in a transcribed sequence (TS) or in a nontranscribed sequence (NTS). The results show that the removal of 8-OxoG in a wild-type MEF cell line is faster in the TS than in the NTS, indicating TCR of 8-OxoG in murine cells. In the homozygous ogg1(-/-) MEF cell line, 8-OxoG was not removed from the NTS whereas there was still efficient 8-OxoG repair in the TS. Expression of the mouse Ogg1 protein in the homozygous ogg1(-/-) cell line restored the ability to remove 8-OxoG in the NTS. Therefore, we have demonstrated that Ogg1 is essential for the repair of 8-OxoG in the NTS but is not required in the TS. These results indicate the existence of an Ogg1-independent pathway for the TCR of 8-OxoG in vivo.

MeSH Terms
Animals Cell Line, Transformed DNA Repair DNA-Formamidopyrimidine Glycosylase Guanine/analogs & derivatives Mice N-Glycosyl Hydrolases/genetics,metabolism Plasmids Transcription, Genetic
Chemicals
8-hydroxyguanine Guanine N-Glycosyl Hydrolases DNA-Formamidopyrimidine Glycosylase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Le Page F
Laboratoire de Radiobiologie de l'ADN, UMR217, Commissariat à l'Energie Atomique-Centre National de la Recherche Scientifique, BP6, 92265-Fontenay aux Roses, France.
Klungland A
Barnes D E
Sarasin A
Boiteux S
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
2000-07-18
Pages
8397-402
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC26959
Subset
IM
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