Collectively these enzymes initiate base excision repair of a large number of base lesions, each recognized by one or a few DNA glycosylases with overlapping specificities. Enzymes that cleave the bond between deoxyribose and a modified or mismatched DNA base are now called DNA glycosylases. Thus, the fundamental steps in the BER pathway were outlined already in the very first paper ( Lindahl 1974). The resulting abasic site (AP-site) was suggested to be further processed by an AP-endonuclease, an exonuclease, a DNA polymerase, and a ligase. Instead, Lindahl identified an enzyme that cleaved the bond between uracil and deoxyribose. Such an activity was found, but rather unexpectedly, it was not a nuclease. Lindahl searched for an enzyme activity that would act on genomic uracil resulting from cytosine deamination.

The identification of Escherichia coli uracil-DNA glycosylase (Ung) in 1974 by Tomas Lindahl marks the discovery of BER. BER takes place in nuclei, as well as in mitochondria, largely using different isoforms of proteins or genetically distant proteins. Much of the damage is the result of spontaneous decay of DNA ( Lindahl 1993), although similar damage may also be caused by environmental chemicals, radiation, or treatment with cytostatic drugs. Such damage typically results from deamination, oxidation, or methylation ( Fig. Base excision repair (BER) corrects small base lesions that do not significantly distort the DNA helix structure.

Mitosis flip book Mrs c