Abstract
Reactive oxygen species (ROS) are produced in cells as by-products of endogenous oxygen metabolism as well as exogenous factors such as ionizing radiation and chemical agents. ROS oxidize biologically important molecules such as nucleic acids, proteins and lipids. The oxidation might be involved in mutagenesis, carcinogenesis and ageing. Among oxidized base lesions, 8-oxo-7,8-dihydroguanine (8-oxo-G) can pair with cytosine and adenine and consequently induces A:T to C:G and G:C to T:A transversion mutations. Organisms developed elaborate mechanisms to prevent the mutagenic effects of 8-oxo-G. Studies on mutator mutants of Escherichia coli elucidated that three enzymes, encoded by the mutM, mutY, and mutT genes, play important roles in avoiding mutagenesis. MutT hydrolyzes 8-oxo-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP) to 8-oxo-dGMP and pyrophosphate. In mammalian cells, similar enzymatic activities have been found, suggesting that similar systems are used to avoid 8-oxo-G-related mutagenesis in mammals. MTH1 has bees identified as human(or mouse)homologue. In this study, we searched candidates for a functional homologue of E. coli MutT in Caenorhabditis elegans and Ciona intestinalis from databases and analyzed their structures and functions.
