Mechanisms of base selection by the Escherichia coli mispaired uracil glycosylase.
Abstract
The repair of the multitude of single-base lesions formed daily in cells of all living organisms is accomplished primarily by the base excision repair pathway that initiates repair through a series of lesion-selective glycosylases. In this article, single-turnover kinetics have been measured on a series of oligonucleotide substrates containing both uracil and purine analogs for the Escherichia coli mispaired uracil glycosylase (MUG). The relative rates of glycosylase cleavage have been correlated with the free energy of helix formation and with the size and electronic inductive properties of a series of uracil 5-substituents. Data are presented that MUG can exploit the reduced thermodynamic stability of mispairs to distinguish U:A from U:G pairs. Discrimination against the removal of thymine results primarily from the electron-donating property of the thymine 5-methyl substituent, whereas the size of the methyl group relative to a hydrogen atom is a secondary factor. A series of parameters have been obtained that allow prediction of relative MUG cleavage rates that correlate well with observed relative rates that vary over 5 orders of magnitude for the series of base analogs examined. We propose that these parameters may be com...Continue Reading
References
Excision of deaminated cytosine from the vertebrate genome: role of the SMUG1 uracil-DNA glycosylase
Mismatch uracil glycosylase from Escherichia coli: a general mismatch or a specific DNA glycosylase?
Mutational analysis of the damage-recognition and catalytic mechanism of human SMUG1 DNA glycosylase
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