Mismatch uracil DNA glycosylase (Mug) from Escherichia coli is an initiating 
enzyme in the base-excision repair pathway. As with other DNA glycosylases, the 
abasic product is potentially more harmful than the initial lesion. Since Mug is 
known to bind its product tightly, inhibiting enzyme turnover, understanding how 
Mug binds DNA is of significance when considering how Mug interacts with 
downstream enzymes in the base-excision repair pathway. We have demonstrated 
differential binding modes of Mug between its substrate and abasic DNA product 
using both band shift and fluorescence anisotropy assays. Mug binds its product 
cooperatively, and a stoichiometric analysis of DNA binding, catalytic activity 
and salt-dependence indicates that dimer formation is of functional significance 
in both catalytic activity and product binding. This is the first report of 
cooperativity in the uracil DNA glycosylase superfamily of enzymes, and forms 
the basis of product inhibition in Mug. It therefore provides a new perspective 
on abasic site protection and the findings are discussed in the context of 
downstream lesion processing and enzyme communication in the base excision 
repair pathway.