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| The EMBO Journal
(2001) 20, 4278–4286, doi:10.1093/emboj/20.15.4278 |
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| Excision of deaminated cytosine from the vertebrate genome: role of the SMUG1 uracil–DNA glycosylase |
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| Hilde Nilsen1, 3, Karl A. Haushalter2, 3, Peter Robins1, Deborah E. Barnes1, Gregory L. Verdine2 and Tomas Lindahl1 |
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1 Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, EN6 3LD, UK 2 Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA 3 H.Nilsen and K.A.Haushalter contributed equally to this work To whom correspondence should be addressed Tomas Lindahl, lindahl@icrf.icnet.uk Received 6 April 2001; Revised 5 June 2001; Accepted 11 June 2001. |
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| Abstract |
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| Gene-targeted mice deficient in the evolutionarily conserved uracil–DNA glycosylase encoded by the UNG gene surprisingly lack the mutator phenotype characteristic of bacterial and yeast ung- mutants. A complementary uracil–DNA glycosylase activity detected in ung-/- murine cells and tissues may be responsible for the repair of deaminated cytosine residues in vivo. Here, specific neutralizing antibodies were used to identify the SMUG1 enzyme as the major uracil–DNA glycosylase in UNG-deficient mice. SMUG1 is present at similar levels in cell nuclei of non-proliferating and proliferating tissues, indicating a replication- independent role in DNA repair. The SMUG1 enzyme is found in vertebrates and insects, whereas it is absent in nematodes, plants and fungi. We propose a model in which SMUG1 has evolved in higher eukaryotes as an anti-mutator distinct from the UNG enzyme, the latter being largely localized to replication foci in mammalian cells to counteract de novo dUMP incorporation into DNA. |
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| Keywords: DNA repair, DNA glycosylases, UNG-deficient cells |
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