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1 2001

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"No Strain, No Gain: " Studies in the Mechanism of a DNA Repair Enzyme

Blackburn G., Walcher G.

Polish Journal of Chemistry

2001

Vol. 75, nr 8

1183-1194

The presence of uracil in DNA occurs either as a result of the mis-incorporation of dUTP in place of dTTP or by deamination of deoxycytidine to give deoxyuridine and is pro-mutagenic. Some 500 such lesions are repaired per cell per day in man. The first enzyme in the repair pathway is uracil DNA glycohydrolase, UDG, which cleaves the glycosylic bond in deoxyuridine in DNA. It shows a rate acceleration of 1012 and specificity for uracil of at least 107 with respect to cytosine or thymine bases. Its mechanism of action has been revealed through the X-ray crystal structure of a transition-state analogue bound in the enzyme active site and is clearly a dissociative, SN1 type process.