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The University of Southampton
Biological Sciences

Research project: Modifying Uracil DNA Glycosylase

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We are generating mutants of this DNA repair enzyme, which have altered recognition properties, and are using these as tools in biotechnological applications.

Uracil-DNA glycosylase (UDGase) selectively recognises and cleaves uracil residues in DNA (which are produced by the mutagenic deamination of cytosine); it does not cleave thymine, which differs from U by the presence of a methyl group in the 5-position. Several structures of this enzyme have been reported and demonstrate that its exquisite selectivity is achieved by a close fit of U, which is not possible with T as the additional methyl group distorts the active site (there is a steric clash with a tyrosine – changing this to a smaller amino acid relaxes this specificity and the mutant enzyme also cleaves T). The structures also reveal specific hydrogen bonds with U, and predict that changing one amino acid (asn123 to asp) will change the hydrogen bonding pattern so that it will recognise C instead generating a cytosine-DNA-glycosylase (CDGase). We are preparing this and other mutants of E. coli and human UDGase, and are examining their selectivity and biochemical properties.

Related research groups

Molecular and Cellular Biosciences
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