Abstract
Reactive oxygen species (ROS) generate various types of oxidative deoxyribonucleotides, such as 8-oxo-dGTP and 8-oxo-dGDP, in the nucleotide pool. 8-oxo-dGTP is generated by both direct oxidation of dGTP and phosphorylation of 8-oxo-dGDP. It is often incorporated into DNA by DNA polymerases during replication, which could result in mutagenic consequences. Many organisms have enzymes for eliminating these abnormal nucleotides in the nucleotide pool as well as repair enzymes for damage in DNA. For example, Escherichia coli MutT and human MTH1 hydrolyze 8-oxo-dGTP, while MutT and human NUDT5 hydrolyze 8-oxo-dGDP to 8-oxo-dGMP, thereby preventing mutations caused by misincorporation of 8-oxo-dGTP into DNA. However, whether there is homolog of these enzymes in the nematode C. elegans, a multicellular eukaryote frequently used as a model for the study of development and aging, has remained uncertain. To clarify the mechanism for eliminating oxidized dNTPs and its critical roles in maintaining the genome stability in C. elegans, we have been studied MutT homolog(s) of C. elegans and recently found that the NDX-1 protein had 8-oxo-dGDPase activity. Although 8-oxo-dGDPase was found in C. elegans, 8-oxo-dGTPase has remained to be identified. As direct oxidation of dGTP also occurs in C. elegans, NDX-1 is not sufficient to fully suppress the generation of 8-oxo-dGTP. Therefore, there must be some mechanism for eliminating 8-oxo-dGTP from the nucleotide pool. So we are investigating enzyme(s) involved in the mechanism. We will show the data obtained in the study.
