Abstract
In human and rodent cells, MTH1, an oxidized purine nucleoside triphosphatase, efficiently hydrolyzes oxidized dGTP, GTP, dATP and ATP such as 2′-deoxy-8-oxoguanosine triphosphate (8-oxo-dGTP) and 2′-deoxy-2-hydroxyadenosine triphosphate (2-OH-dATP) in nucleotide pools, thus avoiding their incorporation into DNA or RNA. MTH1 is expressed in postmitotic neurons as well as in proliferative tissues, and it is localized both in the mitochondria and nucleus, thus suggesting that MTH1 plays an important role in the prevention of the mutagenicity and cytotoxicity of such oxidized purines as 8-oxoG which are known to accumulate in the cellular genome. Our recent studies with MTH1-deficient mice or cells revealed that MTH1 efficiently minimizes accumulation of 8-oxoG in both nuclear and mitochondrial DNA in the mouse brain as well as in cultured cells, thus contributing to the protection of the brain from oxidative stress.
| Original language | English |
|---|---|
| Pages (from-to) | 761-772 |
| Number of pages | 12 |
| Journal | DNA Repair |
| Volume | 5 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Jul 13 2006 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
MTH1, an oxidized purine nucleoside triphosphatase, prevents the cytotoxicity and neurotoxicity of oxidized purine nucleotides. / Nakabeppu, Yusaku; Kajitani, Kosuke; Sakamoto, Katsumi; yamaguchi, hiroo; Tsuchimoto, Daisuke.
In: DNA Repair, Vol. 5, No. 7, 13.07.2006, p. 761-772.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - MTH1, an oxidized purine nucleoside triphosphatase, prevents the cytotoxicity and neurotoxicity of oxidized purine nucleotides
AU - Nakabeppu, Yusaku
AU - Kajitani, Kosuke
AU - Sakamoto, Katsumi
AU - yamaguchi, hiroo
AU - Tsuchimoto, Daisuke
PY - 2006/7/13
Y1 - 2006/7/13
N2 - In human and rodent cells, MTH1, an oxidized purine nucleoside triphosphatase, efficiently hydrolyzes oxidized dGTP, GTP, dATP and ATP such as 2′-deoxy-8-oxoguanosine triphosphate (8-oxo-dGTP) and 2′-deoxy-2-hydroxyadenosine triphosphate (2-OH-dATP) in nucleotide pools, thus avoiding their incorporation into DNA or RNA. MTH1 is expressed in postmitotic neurons as well as in proliferative tissues, and it is localized both in the mitochondria and nucleus, thus suggesting that MTH1 plays an important role in the prevention of the mutagenicity and cytotoxicity of such oxidized purines as 8-oxoG which are known to accumulate in the cellular genome. Our recent studies with MTH1-deficient mice or cells revealed that MTH1 efficiently minimizes accumulation of 8-oxoG in both nuclear and mitochondrial DNA in the mouse brain as well as in cultured cells, thus contributing to the protection of the brain from oxidative stress.
AB - In human and rodent cells, MTH1, an oxidized purine nucleoside triphosphatase, efficiently hydrolyzes oxidized dGTP, GTP, dATP and ATP such as 2′-deoxy-8-oxoguanosine triphosphate (8-oxo-dGTP) and 2′-deoxy-2-hydroxyadenosine triphosphate (2-OH-dATP) in nucleotide pools, thus avoiding their incorporation into DNA or RNA. MTH1 is expressed in postmitotic neurons as well as in proliferative tissues, and it is localized both in the mitochondria and nucleus, thus suggesting that MTH1 plays an important role in the prevention of the mutagenicity and cytotoxicity of such oxidized purines as 8-oxoG which are known to accumulate in the cellular genome. Our recent studies with MTH1-deficient mice or cells revealed that MTH1 efficiently minimizes accumulation of 8-oxoG in both nuclear and mitochondrial DNA in the mouse brain as well as in cultured cells, thus contributing to the protection of the brain from oxidative stress.
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UR - http://www.scopus.com/inward/citedby.url?scp=33745257002&partnerID=8YFLogxK
U2 - 10.1016/j.dnarep.2006.03.003
DO - 10.1016/j.dnarep.2006.03.003
M3 - Review article
C2 - 16621731
AN - SCOPUS:33745257002
VL - 5
SP - 761
EP - 772
JO - DNA Repair
JF - DNA Repair
SN - 1568-7864
IS - 7
ER -