Excision by Enzymatic Hydrolysis

As mentioned briefly above, the enzymatic excision of damaged nucleobases may cause some problems. A case in point is the action of nuclease PI. While a single 8-oxo-G lesion is excised as the damaged nucleoside, the clustered 8-oxo-G/Fo lesion is only obtained as modified dinucleotide (Maccubbin et al. 1992). Another example is the hydrolysis of dG pC which severely inhibits the action of bovine spleen phosphodiesterase, while HMUrapA shows only very little inhibition (Maccubbin et al. 1991). Enzymatic hydrolysis of DNA is, in fact, the recommended method for the determination of HMUra (Teebor et al. 1984 Frenkel et al. 1985). It is recalled that mammalian cells cope with this DNA lesion with the help of a hydroxymethyluracil glycosylase (Hollstein et al. 1984). 

When the Tg lesions is opened by ammonolysis, the resulting product ( x-iMiydroxy-P-ureidoisobutyric acid) inhibits snake venom phosphodiesterase, A exonuclease and the Klenow (exo ) fragment (Matray et al. 1995 see also Greenberg and Matray 1997). It is, however, removed by E. coli Fpg and Nth proteins (Jurado et al. 1998). 

The development in this area of enzymatic action on the various damaged DNA sites continues to be very active. For this reason, only a very short account has been given as a kind of flavor for the reader to see in which direction research in this field seems to expand. 

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