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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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.
The authors declare no competing financial interests.
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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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