Response to Comment on "Uracil DNA Glycosylase Activity Is Dispensable for Immunoglobulin Class Switch"

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Abstract
To explain the result that Ugi blocked CSR but not the introduction of DSBs, Stivers proposes that Ugi cannot completely block the enzymatic activity of mUNG for promoting DSBs, but can block complex formation with other proteins required for DNA repair. He also cites a study showing that Ugi has a relatively weaker affinity to human UNG than to E. coli UNG (6). However, Ugi has previously been shown to completely block human UNG activity (6, 7). We also confirmed that Ugi-expressing CH12 cell extracts can inhibit recombinant UNG in vitro, which indicates that Ugi is present in excess. Furthermore, if Stivers' view is correct, it would demand reevaluation of the original paper proposing the DNA deamination model, in which Neuberger et al. used Ugi to inhibit UNG in a DT40 cell line (8).