Reactive oxygen species are produced as side products of oxygen utilization and 
can lead to the oxidation of nucleic acids and their precursor nucleotides. 
Among the various oxidized bases, 8-oxo-7,8-dihydroguanine seems to be the most 
critical during the transfer of genetic information because it can pair with 
both cytosine and adenine. During the de novo synthesis of guanine nucleotides, 
GMP is formed first, and it is converted to GDP by guanylate kinase. This enzyme 
hardly acts on an oxidized form of GMP (8-oxo-GMP) formed by the oxidation of 
GMP or by the cleavage of 8-oxo-GDP and 8-oxo-GTP by MutT protein. Although the 
formation of 8-oxo-GDP from 8-oxo-GMP is thus prevented, 8-oxo-GDP itself may be 
produced by the oxidation of GDP by reactive oxygen species. The 8-oxo-GDP thus 
formed can be converted to 8-oxo-GTP because nucleoside-diphosphate kinase and 
adenylate kinase, both of which catalyze the conversion of GDP to GTP, do not 
discriminate 8-oxo-GDP from normal GDP. The 8-oxo-GTP produced in this way and 
by the oxidation of GTP can be used for RNA synthesis. This misincorporation is 
prevented by MutT protein, which has the potential to cleave 8-oxo-GTP as well 
as 8-oxo-GDP to 8-oxo-GMP. When (14)C-labeled 8-oxo-GTP was applied to 
CaCl2-permeabilized cells of a mutT(-) mutant strain, it could be incorporated 
into RNA at 4% of the rate for GTP. Escherichia coli cells appear to possess 
mechanisms to prevent misincorporation of 8-oxo-7,8-dihydroguanine into RNA.