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Base-excision repair of oxidative DNA damage

Nature volume 447, pages 941–950 (2007)Cite this article

Abstract

Maintaining the chemical integrity of DNA in the face of assault by oxidizing agents is a constant challenge for living organisms. Base-excision repair has an important role in preventing mutations associated with a common product of oxidative damage to DNA, 8-oxoguanine. Recent structural studies have shown that 8-oxoguanine DNA glycosylases use an intricate series of steps to locate and excise 8-oxoguanine lesions efficiently against a high background of undamaged bases. The importance of preventing mutations associated with 8-oxoguanine is shown by a direct association between defects in the DNA glycosylase MUTYH and colorectal cancer. The properties of other guanine oxidation products and the associated DNA glycosylases that remove them are now also being revealed.

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Figure 1: Short-patch BER pathway for 8-oxoG.
Figure 2: Structures of 8-oxoG-containing base pairs and of several nucleosides of guanine oxidation products.
Figure 3: Recognition of 8-oxoG by OGG1 observed in the LRC of OGG1 with 8-oxoG·C-containing duplexes.
Figure 4: The LRCs of OGG1 and MutM with non-specific complexes (normal base pairs).
Figure 5: The 8-oxoG lesion search process.
Figure 6: Germline mutations observed in MUTYH in individuals with MUTYH-associated polyposis.

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Acknowledgements

We thank members of the David laboratory for reading the manuscript. We also apologize to all scientists whose original studies and reviews were not included because of space limitations. Research in the laboratory of S.S.D. is funded by the National Institutes of Health, and V.L.O. has been supported by pre-doctoral fellowships from the National Institutes of Health.

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  1. Department of Chemistry, University of California at Davis, 1 Shields Avenue, Davis, 95616, California, USA

    Sheila S. David

  2. Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, 84112, Utah, USA

    Valerie L. O'Shea & Sucharita Kundu

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David, S., O'Shea, V. & Kundu, S. Base-excision repair of oxidative DNA damage. Nature 447, 941–950 (2007). https://doi.org/10.1038/nature05978

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