Uracil-DNA-glycosidases

Figure 11.8. Activities of enzymes that remove inappropriate bases from DNA. The specific activities of uracil DNA glycosidase (black bars) and thymine DNA glycosidase (open bars) were measured in extracts of colon mucosa. Extracts were prepared from seven normal human subjects (subjects A to G). To the extracts were added synthetic strands of double-stranded DNA that contained a mismatched U G pair or a mismatched T G pair. The unit of specific activity used was nmol/mg protein/min. The results show, at least in tissue extracts, that the removal of U occurs at a dramatically greater rate than the removal ofT.

Uracil DNA glycosidase is a DNA repair enzyme which removes the non-DNA base uracil from double-stranded DNA. A pre-steady-state analysis using a fluorescent 2-aminopyridine-uracil mismatch and the E. coli enzyme suggested that the enzyme first bound substrate non-specifically with a... 

Uracil is removed from the DNA by a uracil glycosidase which excises the base from the sugar ring. This activity is analogous to the hydrolytic activity of the isoleucyl-tRNA synthetase toward Val-tRNAIle. In both cases the hydrolytic site is too small by the size of one methylene group to accommodate the substrate that is to be left intact. In DNA synthesis, the editing is performed by a separate enzyme, since the editing can wait until after polymerization. As this luxury is not permitted in protein synthesis, the hydrolytic function is on the synthetase, so that correction can occur before the misacylated tRNA leaves the enzyme. 

Lindahl T (1974) An N-glycosidase from Escherichia coli that releases free uracil from DNA containing deaminated cytosine residues. Proc Natl Acad Sci USA 71 3649-53... 

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