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Uracil in DNA – occurrence, consequences and repair

Oncogene volume 21, pages 8935–8948 (2002)Cite this article

Abstract

Uracil in DNA results from deamination of cytosine, resulting in mutagenic U : G mispairs, and misincorporation of dUMP, which gives a less harmful U : A pair. At least four different human DNA glycosylases may remove uracil and thus generate an abasic site, which is itself cytotoxic and potentially mutagenic. These enzymes are UNG, SMUG1, TDG and MBD4. The base excision repair process is completed either by a short patch- or long patch pathway, which largely use different proteins. UNG2 is a major nuclear uracil-DNA glycosylase central in removal of misincorporated dUMP in replication foci, but recent evidence also indicates an important role in repair of U : G mispairs and possibly U in single-stranded DNA. SMUG1 has broader specificity than UNG2 and may serve as a relatively efficient backup for UNG in repair of U : G mismatches and single-stranded DNA. TDG and MBD4 may have specialized roles in the repair of U and T in mismatches in CpG contexts. Recently, a role for UNG2, together with activation induced deaminase (AID) which generates uracil, has been demonstrated in immunoglobulin diversification. Studies are now underway to examine whether mice deficient in Ung develop lymphoproliferative malignancies and have a different life span.

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Acknowledgements

This work was sponsored by The Norwegian Cancer Society, The Research Council of Norway, The Cancer Fund at the St. Olavs Hospital, Trondheim and The Svanhild and Arne Must Fund for Medical Research.

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  1. Institute of Cancer Research and Molecular Biology, Norwegian University of Science and Technology, Trondheim, N-7489, Norway

    Hans E Krokan, Finn Drabløs & Geir Slupphaug

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Correspondence to Hans E Krokan.

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Krokan, H., Drabløs, F. & Slupphaug, G. Uracil in DNA – occurrence, consequences and repair. Oncogene 21, 8935–8948 (2002). https://doi.org/10.1038/sj.onc.1205996

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