MutT-related proteins, including the Escherichia coli MutT and human MutT 
homologue 1 (MTH1) proteins, degrade 8-oxo- 7,8-dihydrodeoxyguanosine 
triphosphate (8-oxo-dGTP) to a monophosphate, thereby preventing mutations 
caused by the misincorporation of 8-oxoguanine into DNA. Here, we report that 
human cells have another mechanism for cleaning up the nucleotide pool to ensure 
accurate DNA replication. The human Nudix type 5 (NUDT5) protein hydrolyses 
8-oxo-dGDP to monophosphate with a K(m) of 0.77 microM, a value considerably 
lower than that for ADP sugars, which were originally identified as being 
substrates of NUDT5. NUDT5 hydrolyses 8-oxo-dGTP only at very low levels, but is 
able to substitute for MutT when it is defective. When NUDT5 is expressed in E. 
coli mutT(-) cells, the increased frequency of spontaneous mutations is 
decreased to normal levels. Considering the enzymatic parameters of MTH1 and 
NUDT5 for oxidized guanine nucleotides, NUDT5 might have a much greater role 
than MTH1 in preventing the occurrence of mutations that are caused by the 
misincorporation of 8-oxoguanine in human cells.