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  • Original Paper
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Global genome repair of 8-oxoG in hamster cells requires a functional CSB gene product

Oncogene volume 21, pages 3571–3578 (2002)Cite this article

Abstract

Cockayne syndrome (CS) is an autosomal recessive human disease characterized by UV-sensitivity as well as neurological and developmental abnormalities. Two complementation groups have been established, designated CS-A and CS-B. Traditionally, CSA and CSB have been ascribed a function in the transcription-coupled repair (TCR) pathway of nucleotide excision repair (NER) that efficiently removes bulky lesions from the transcribed strand of RNA polymerase II transcribed genes. To assess the role of the CSB protein in the repair of the highly mutagenic base lesion 7,8-dihydro-8-oxoguanine (8-oxoG), we have investigated the removal of this lesion using an in vitro incision approach with cell extracts as well as an in vivo approach with a modified protocol of the gene-specific repair assay, which allows the measurement of base lesion repair in intragenomic sequences. Our results demonstrate that the integrity of the CSB protein is pivotal for processes leading to incision at the site of 8-oxoG and that the global genome repair (GGR) of this lesion requires a functional CSB gene product in vivo.

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Acknowledgements

We appreciate the comments by T Thorslund and the technical assistance by UB Henriksen. RO19-8022 was a gift from Hoffman la Roche AG (Basel, Switzerland) and S Boiteux kindly provided the Fpg enzyme. TS was supported by The Danish Research Council and MS was supported by EU grant (QLK6-CT-1999-02002). The Novo Nordic Foundation, Eva and Henry Frænkels Foundation, and the foundation of 17.12.1981 supported the project.

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Author notes

  1. Morten Sunesen

    Present address: Laboratoire de Neurobiologie Moleculaire, Centre National de la Recherche Scientifique, Unite de Recherche Associee 2182, Institut Pasteur, 28 Rue du Dr. Roux, Paris, Cedex 15, 75724, France

Authors and Affiliations

  1. Department of Molecular and Structural Biology, University of Aarhus, Aarhus C, DK-8000, Denmark

    Morten Sunesen & Tinna Stevnsner

  2. Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, 21224, Maryland, MD, USA

    Robert M Brosh Jr, Grigory L Dianov & Vilhelm A Bohr

  3. MRC Radiation and Genome Stability Unit, Medical Research Council, Harwell, OX11, Oxfordshire, ORD, UK

    Grigory L Dianov

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  1. Morten Sunesen
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Correspondence to Vilhelm A Bohr.

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Sunesen, M., Stevnsner, T., Brosh Jr, R. et al. Global genome repair of 8-oxoG in hamster cells requires a functional CSB gene product. Oncogene 21, 3571–3578 (2002). https://doi.org/10.1038/sj.onc.1205443

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