Enzymatic Studies of Base Excision Repair in Cultured Human Fibroblasts and in Escherichia coli

With the discovery some six years ago of uracil DNA glycosylase by Lindahl,1 it became possible to define a new mode of excision repair, “base excision repair,”2 which was hypothesized to occur by (i) removal of a DNA base by hydrolysis of the glycosylic bond, (ii) cleavage of a phosphodiester bond adjacent to the resulting apurinic/ apyrimidinic (AP) site by an “AP endonuclease,” and (iii) subsequent excision of the sugar and resynthesis by DNA polymerase. In the past few years it has been the goal of our laboratory to study the base-excision processes in depth in order to determine exactly the sequence and mechanisms of the enzymatic events involved, and the relation of this repair mode to nucleotide excision repair processes. This article summarizes some of the recent studies from our laboratory toward this goal. Space considerations prevent a review of related studies from other laboratories and such an omission should not be taken to indicate that our results are particularly unique. Indeed we encourage the reader to consult articles on similar endeavors that are found elsewhere in this volume as well as to consult Lindahl’s recent comprehensive review.3