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Yusaku Nakabeppu Last modified date:2017.02.23

Professor / Division of Neurofunctional Genoimics
Department of Immunobiology and Neuroscience
Medical Institute of Bioregulation


Graduate School
Undergraduate School
Other Organization
Administration Post
Director of the Medical Institute of Bioregulation


E-Mail
Homepage
http://www.bioreg.kyushu-u.ac.jp/nfg/index.html
Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University .
Phone
092-642-6800
Fax
092-642-6791
Academic Degree
Doctor of Science
Field of Specialization
Neurofunctional Genoimics, Molecular Neuroscience, Biochemistry, Molecular Biology, Molecular Carcinogenesis
Outline Activities
The genomic DNA and its precursor nucleotides are always in danger of oxidation by reactive oxygen species (ROS) which are produced during the oxygen respiration and other normal metabolisms. Various oxidized bases and nucleotides are formed in DNA or nucleotide pools by ROS, and such oxidative lesions in nucleic acids cause mutations or cell death if they are not repaired or eliminated. Mutations induce cancers, and cell death is related to various neurodegenerative diseases, such as Parkinson’s and Alzheimer’s diseases.

By analyzing the cell fate to either proliferate, arrest cell growth or initiate programmed cell death under oxidative stress, we have unveiled the mechanisms protecting genomic integrity from damage caused by ROS. Recently, we have shown that Fosb-null mice display impaired adult hippocampal neurogenesis and spontaneous epilepsy with depressive behavior and that Fosb-null mouse is the first animal model to provide a genetic and molecular basis for the comorbidity between depression and epilepsy with abnormal neurogenesis, all of which are caused by loss of a single gene, Fosb.

Moreover, we reported that neurodegeneration is triggered by MUTYH-mediated excision repair of 8-oxoG-paired adenine. Mutant mice lacking 8-oxo-2‘-deoxyguanosine triphosphate-depleting (8-oxo-dGTP-depleting) MTH1 and/or 8-oxoG-excising OGG1 exhibited severe striatal neurodegeneration, whereas mutant mice lacking MUTYH or OGG1/MUTYH were resistant to neurodegeneration under conditions of oxidative stress. These results indicate that OGG1 and MTH1 are protective, while MUTYH promotes neurodegeneration. We observed that 8-oxoG accumulated in the mitochondrial DNA of neurons and caused calpain-dependent neuronal loss, while delayed nuclear accumulation of 8-oxoG in microglia resulted in PARP-dependent activation of apoptosis-inducing factor and exacerbated microgliosis. These results revealed that neurodegeneration is a complex process caused by 8-oxoG accumulation in the genomes of neurons and microglia. Different signaling pathways were triggered by the accumulation of single-strand breaks in each type of DNA generated during base excision repair initiated by MUTYH, suggesting that suppression of MUTYH may protect the brain under conditions of oxidative stress. We also demonstrated that MTH1 attenuates oxidative DNA damage and delays photoreceptor cell death in inherited retinal degeneration by sanitizing nucleotide pool in the photoreceptor cells.

Diabetes mellitus (DM) is considered to be a risk factor for dementia including Alzheimer's disease (AD). However, the molecular mechanism underlying this risk is not well understood. We examined gene expression profiles in postmortem human brains donated for the Hisayama study. Three-way analysis of variance of microarray data from frontal cortex, temporal cortex, and hippocampus was performed with the presence/absence of AD and vascular dementia, and sex, as factors. Comparative analyses of expression changes in the brains of AD patients and a mouse model of AD were also performed. Relevant changes in gene expression identified by microarray analysis were validated by quantitative real-time reverse-transcription polymerase chain reaction and western blotting. The hippocampi of AD brains showed the most significant alteration in gene expression profile. Genes involved in noninsulin-dependent DM and obesity were significantly altered in both AD brains and the AD mouse model, as were genes related to psychiatric disorders and AD. The alterations in the expression profiles of DM-related genes in AD brains were independent of peripheral DM-related abnormalities. These results indicate that altered expression of genes related to DM in AD brains is a result of AD pathology, which may thereby be exacerbated by peripheral insulin resistance or DM.
Research
Research Interests
  • Genetic risk factors for Alzheimer Disease, and their molecular mechanisms
    keyword : dementia, gene expression profiling, postmorten brains, animal model, iPS cells
    2008.04For living organisms, the most fundamental biological function is maintaining the integrity of their genomic DNAs harboring the genetic information and transmitting them precisely from cell to cell, as well as from parents to their offsprings. The genomic DNA and its precursor nucleotides, are always in danger of oxidation by reactive oxygen species (ROS)which are produced during the oxygen respiration and other normal metabolisms. Various oxidized bases and nucleotides are formed in DNA or nucleotide pools by the reactive oxygen species, and such oxidative DNA damage may cause mutations or cell death if they are not repaired. Mutations may induce cancers, and cell death may be related to various degenerative diseases. On the other hand, the regulation of the cell fate to either proliferate, differentiate, arrest cell growth or initiate programmed cell death is the most fundamental mechanism to maintain a normal cell function and tissue homeostasis in mammals. In our division, we are trying to unveil the mechanisms protecting genomic integrity from damage caused by reactive oxygen species. We are especially focusing on neuronal cell death as a consequence of oxidative damages in non-proliferative cells, as well as on cancer that is a consequence of such damages in proliferative cells. We are furthermore characterizing signal molecules and transcription factors, which regulate gene expression in neurons or brain under oxidative stress, and their targets in order to explore the molecular mechanisms underlying determination of neuronal fate such as proliferation and differentiation of neuronal stem cells and neuronal cell death, thus establishing a new research field of neurofunctional genomics..
  • Regulatory mechanisms of brain function by alternative splice products of fosB gene
    keyword : Alternative splicing, transcription regulation, neurogenesis, mode disorder, epilepsy
    2011.04For living organisms, the most fundamental biological function is maintaining the integrity of their genomic DNAs harboring the genetic information and transmitting them precisely from cell to cell, as well as from parents to their offsprings. The genomic DNA and its precursor nucleotides, are always in danger of oxidation by reactive oxygen species (ROS)which are produced during the oxygen respiration and other normal metabolisms. Various oxidized bases and nucleotides are formed in DNA or nucleotide pools by the reactive oxygen species, and such oxidative DNA damage may cause mutations or cell death if they are not repaired. Mutations may induce cancers, and cell death may be related to various degenerative diseases. On the other hand, the regulation of the cell fate to either proliferate, differentiate, arrest cell growth or initiate programmed cell death is the most fundamental mechanism to maintain a normal cell function and tissue homeostasis in mammals. In our division, we are trying to unveil the mechanisms protecting genomic integrity from damage caused by reactive oxygen species. We are especially focusing on neuronal cell death as a consequence of oxidative damages in non-proliferative cells, as well as on cancer that is a consequence of such damages in proliferative cells. We are furthermore characterizing signal molecules and transcription factors, which regulate gene expression in neurons or brain under oxidative stress, and their targets in order to explore the molecular mechanisms underlying determination of neuronal fate such as proliferation and differentiation of neuronal stem cells and neuronal cell death, thus establishing a new research field of neurofunctional genomics..
  • Molecular pathology and regulatory mechanisms involved in the breakdown of nucleotide pool homeostasis under environmental stress
    keyword : damage, nucleotide pool, DNA, RNA
    2010.04~2015.03For living organisms, the most fundamental biological function is maintaining the integrity of their genomic DNAs harboring the genetic information and transmitting them precisely from cell to cell, as well as from parents to their offsprings. The genomic DNA and its precursor nucleotides, are always in danger of oxidation by reactive oxygen species (ROS)which are produced during the oxygen respiration and other normal metabolisms. Various oxidized bases and nucleotides are formed in DNA or nucleotide pools by the reactive oxygen species, and such oxidative DNA damage may cause mutations or cell death if they are not repaired. Mutations may induce cancers, and cell death may be related to various degenerative diseases. On the other hand, the regulation of the cell fate to either proliferate, differentiate, arrest cell growth or initiate programmed cell death is the most fundamental mechanism to maintain a normal cell function and tissue homeostasis in mammals. In our division, we are trying to unveil the mechanisms protecting genomic integrity from damage caused by reactive oxygen species. We are especially focusing on neuronal cell death as a consequence of oxidative damages in non-proliferative cells, as well as on cancer that is a consequence of such damages in proliferative cells. We are furthermore characterizing signal molecules and transcription factors, which regulate gene expression in neurons or brain under oxidative stress, and their targets in order to explore the molecular mechanisms underlying determination of neuronal fate such as proliferation and differentiation of neuronal stem cells and neuronal cell death, thus establishing a new research field of neurofunctional genomics..
  • Study on the mechanisms protecting genomic integrity from damage caused by reactive oxygen species
    keyword : oxidative DNA damage, oxidized nucleotide, genome damage, mitochondria, mutation, cell death, galectin-1, signal transduction, immediate early genes, carcinogenesis, brain aging, immunodeficiency
    2003.12For living organisms, the most fundamental biological function is maintaining the integrity of their genomic DNAs harboring the genetic information and transmitting them precisely from cell to cell, as well as from parents to their offsprings. The genomic DNA and its precursor nucleotides, are always in danger of oxidation by reactive oxygen species (ROS)which are produced during the oxygen respiration and other normal metabolisms. Various oxidized bases and nucleotides are formed in DNA or nucleotide pools by the reactive oxygen species, and such oxidative DNA damage may cause mutations or cell death if they are not repaired. Mutations may induce cancers, and cell death may be related to various degenerative diseases. On the other hand, the regulation of the cell fate to either proliferate, differentiate, arrest cell growth or initiate programmed cell death is the most fundamental mechanism to maintain a normal cell function and tissue homeostasis in mammals. In our division, we are trying to unveil the mechanisms protecting genomic integrity from damage caused by reactive oxygen species. We are especially focusing on neuronal cell death as a consequence of oxidative damages in non-proliferative cells, as well as on cancer that is a consequence of such damages in proliferative cells. We are furthermore characterizing signal molecules and transcription factors, which regulate gene expression in neurons or brain under oxidative stress, and their targets in order to explore the molecular mechanisms underlying determination of neuronal fate such as proliferation and differentiation of neuronal stem cells and neuronal cell death, thus establishing a new research field of neurofunctional genomics..
Academic Activities
Books
1. Nakabeppu Y, Neurodegeneration caused by accumulation of an oxidized base lesion, 8-oxoguanine, in nuclear and mitochondrial DNA: from animal models to human diseases, in The Base Excision Repair Pathway: Molecular Mechanisms and Role in Disease Development and Therapeutic Strategies, David M Wilson III, Editor, World Scientific Publishing, Chapter 14, pp.523-556, 2017.01.
2. Oka, S., Ohno, M., and Nakabeppu, Y., Construction and characterization of a cell line deficient in repair of mitochondrial, but not nuclear, oxidative DNA damage. In Mitochondrial DNA, Methods and Protocols, (J.A. Stuart, ed.), Humana Press, New York, Methods Mol Biol 544: 251-264., 2009.07.
3. Ohno, M., Oka, S., and Nakabeppu, Y. , Quantitative analysis of oxidized guanine, 8-oxoguanine, in mitochondrial DNA by immunofluorescence method. In Mitochondrial DNA, Methods and Protocols, (J.A. Stuart, ed.), Humana Press, New York, Methods Mol Biol 544: 199-212, 2009.07.
4. Nakabeppu, Y., Behmanesh, M., Yamaguchi, H., Yoshimura, D., and Sakumi, K. , Prevention of the mutagenecity and cytotoxicity of oxidized purine nucleotides, In Oxidative Damage to Nucleic Acids, (M. D. Evans, and M. S. Cooke, eds. ), Landes Bioscience, Austin, Texas, USA & Springer Science + Business Media, New York, New York, USA., Chapter 3, p40-53., 2007.07.
5. Nakabeppu, Y., Maki, H., and Sekiguchi, M. , DNA Replication and Transcription: In Genomics and Genetics: From Molecular Details to Analysis and Techniques (Meyers, R.A. ed.), Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany., Vol. 1: pp. 47-73, 2007.02.
Reports
1. Yusaku Nakabeppu, Eiko Ohta, Nona Abolhassani, MTH1 as a nucleotide pool sanitizing enzyme: friend or foe?, Free Radic Biol Med, pii: S0891-5849(16)31031-0. doi: 10.1016/j.freeradbiomed.2016.11.002., 2017.04.
2. Arikuni Uchimura, Yuichiro Hara, Yoichi Gondo, Yusaku Nakabeppu, International Symposium on “Germline Mutagenesis and Biodiversification”, Genes Genet. Syst., Genes Genet Syst. 2014;89(2):93-95., 2014.09.
3. Yusaku Nakabeppu, Cellular Levels of 8-Oxoguanine in either DNA or the Nucleotide Pool Play Pivotal Roles in Carcinogenesis and Survival of Cancer Cells, Int J Mol Sci. 2014, 15(7):12543-12557. doi: 10.3390/ijms150712543., 2014.07, [URL].
4. Fujita K, Yamafuji M., Yusaku Nakabeppu, MAMI NODA, Therapeutic approach to neurodegenerative diseases by medical gases: focusing on redox signaling and related antioxidant enzymes, Oxid Med Cell Longev. 2012:324256. , doi: 10.1155/2012/324256. , 2012.07.
5. 作見 邦彦, 土本 大介, 中別府 雄作, ニトロソ化ストレスによるイノシン三リン酸の生成と細胞応答, 細胞工学 Vol. 31: 175-180, 2012.01.
6. Oka S, Nakabeppu Y., DNA glycosylase encoded by MUTYH functions as a molecular switch for programmed cell death under oxidative stress to suppress tumorigenesis, Cancer Sci. 2011;102(4):677-682. , 2011.04.
7. Kyota Fujita, Yusaku Nakabeppu, and Mami Noda, Therapeutic Effects of Hydrogen in Animal Models of Parkinson’s Disease, Parkinsons Dis. 2011:307875, 2011.04.
8. Ihara H, Sawa T, Nakabeppu Y, Akaike T., Nucleotides function as endogenous chemical sensors for oxidative stress signaling, J Clin Biochem Nutr. 2011;48(1):33-39, 2011.01.
9. Nakabeppu Y., Oka S., Sheng Z., Tsuchimoto D., Sakumi K. , Programmed cell death triggered by nucleotide pool damage and its prevention by MutT homolog-1 (MTH1) with oxidized purine nucleoside triphosphatase. , Mutation Research, 2010.06.
10. Tsuchimoto D., Iyama T., Nonaka M., Abolhassani N., Ohta E., Sakumi K., Nakabeppu Y., A comprehensive screening system for damaged nucleotide-binding proteins., Mutation Research, 2010.06.
11. Sakumi K., Abolhassani N., Behmanesh M., Iyama T., Tsuchimoto D., Nakabeppu Y., ITPA protein, an enzyme that eliminates deaminated purine nucleoside triphosphates in cells., Mutation Research, 2010.06.
12. Yusaku Nakabeppu, Daisuke Tsuchimoto, Hiroo Yamaguchi and Kunihiko Sakumi, Oxidative Damage in Nucleic Acids and Parkinson's Disease, Journal of Neuroscience Research, 85(5):919-934. , 2007.04.
13. Yusaku Nakabeppua, Kosuke Kajitani, Katsumi Sakamoto, Hiroo Yamaguchi, Daisuke Tsuchimoto, MTH1, an oxidized purine nucleoside triphosphatase, prevents the cytotoxicity and neurotoxicity of oxidized purine nucleotides, DNA Repair, Vol. 5(7): 761-772, 2006.07.
14. Nakabeppu Y., Sakumi K., Sakamoto K., Tsuchimoto D., Tsuzuki T., Nakatsu Y., Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids., Biol. Chem., Vol. 387: 373-379., 2006.04.
Papers
1. Nona Abolhassani, Julio Leon, Zijing Sheng, Sugako Oka, Hideomi Hamasaki, Toru Iwaki, Yusaku Nakabeppu, Molecular pathophysiology of impaired glucose metabolism, mitochondrial dysfunction, and oxidative DNA damage in Alzheimer's disease brain, Mech Ageing Dev, 161, 2017.02.
2. Sugako Oka, Julio Leon, Kunihiko Sakumi, Tomomi Ide, Dongchon Kang, Frank M LaFerla, Yusaku Nakabeppu, Human mitochondrial transcriptional factor A breaks the mitochondria-mediated vicious cycle in Alzheimer’s disease, Sci Rep, 6, 2016.11, [URL].
3. Michel Massaad, Jia Zhou, Daisuke Tsuchimoto, Janet Chou, Haifa Jabara, Erin Janssen, Salome Glauzy, Brennan G. Olson, Henner Morbach, Toshiro Ohsumi, Klaus SchmitzAbe, Markianos Kyriacos, Jennifer Kane, Kumiko Torisu, Yusaku Nakabeppu, Luigi D. Notarangelo, Eliane Chouery, André Megarbane, Peter B. Kang, Deficiency of the base excision repair enzyme NEIL3 is associated with increased lymphocyte apoptosis, autoantibodies and predisposition to autoimmunity, J Clin Invest, 126, 11, 2016.11.
4. Kumiko Torisu, Xueli Zhang, Mari Nonak, Takahide Kaji, Daisuke Tsuchimoto, Kosuke Kajitani, SAKUMI Kunihiko, Torisu Takehiro, Kazuhiro Chida, Katsuo Sueishi, Michiaki Kubo, Jun Hata, Kitazono T, Yutaka Kiyohara, Yusaku Nakabeppu, PKCη deficiency improves lipid metabolism and atherosclerosis in apolipoprotein E-deficient mice, Genes to Cells, 21, 10, 2016.10.
5. Yasuto Yoneshima, Nona Abolhassani, Teruaki Iyama, Kunihiko Sakumi, Naoko Shiomi, Masahiko Mori, Tadahiro Shiomi, Tetsuo Noda, Daisuke Tsuchimoto, Yusaku Nakabeppu, Deoxyinosine triphosphate induces MLH1/PMS2- and p53-dependent cell growth arrest and DNA instability in mammalian cells, Sci Rep, 6, 2016.09.
6. Shunji Nakatake, Yusuke Murakami, Yasuhiro Ikeda, Noriko Morioka, Takashi Tachibana, Kohta Fujiwara, Noriko Yoshida, Shoji Notomi, Toshio Hisatomi, Shigeo Yoshida, Tatsuro Ishibashi, Yusaku Nakabeppu, Koh-Hei Sonoda, MUTYH promotes oxidative microglial activation and inherited retinal degeneration, JCI Insight, 1, 15, 2016.09.
7. Julio Leon, Kunihiko Sakumi, Erika Castillo, Zijing Sheng, Sugako Oka, Yusaku Nakabeppu, 8-Oxoguanine accumulation in mitochondrial DNA causes mitochondrial dysfunction and impairs neuritogenesis in cultured adult mouse cortical neurons under oxidative conditions., Sci Rep, 6, 2016.02.
8. Bjorge, Monica D, Hildrestrand, Gunn A, Scheffler, Katja, Suganthan, Rajikala, Rolseth, Veslemoy, Kusnierczyk, Anna, Rowe, Alexander D, Vagbo, Cathrine B, Vetlesen, Susanne, Eide, Lars, Slupphaug, Geir, Nakabeppu, Yusaku, Bredy, Timothy W, Klungland, Arne, Bjoras, Magnar, Synergistic Actions of Ogg1 and Mutyh DNA Glycosylases Modulate Anxiety-like Behavior in Mice, Cell Reports, 13, 12, 2671-2678, 2015.12.
9. Yuko Kobayakawa, Kunihiko Sakumi, Kosuke Kajitani, Toshihiko Kadoya, Hidenori Horie, Jun-ichi Kira, Yusaku Nakabeppu, Galectin-1 deficiency improves axonal swelling of motor neurons in SOD1G93A transgenic mice, Neuropathol Appl Neurobiol, 41, 2, 2015.02.
10. Sugako Oka, Julio Leon, Daisuke Tsuchimoto, Kunihiko Sakumi, Yusaku Nakabeppu, MUTYH, an adenine DNA glycosylase, mediates p53 tumor suppression via PARP-dependent cell death, Oncogenesis, 3, 2014.10, [URL].
11. Masaaki Hokama, Sugako Oka, Julio Leon, Toshiharu Ninomiya, HIROYUKI HONDA, Kensuke Sasaki, Toru Iwaki, Tomoyuki Ohara, Tomio Sasaki, Frank M. LaFerla, Yutaka Kiyohara, Yusaku Nakabeppu, Altered expression of diabetes-related genes in Alzheimer’s disease brains: The Hisayama study, Cereb Cortex , 24, 9, 2014.09.
12. Hiroko Nomaru, Kunihiko Sakumi, Atsuhisa Katogi, Yoshinori N Ohnishi, Kosuke Kajitani, Daisuke Tsuchimoto, Eric J. Nestler, Yusaku Nakabeppu, Fosb gene products contribute to excitotoxic microglial activation by regulating the expression of complement C5a receptors in microglia, Glia, 62, 8, 2014.08.
13. Hideomi Hamasaki, Hiroyuki Honda, Satoshi O Suzuki, Masaaki Hokama, Yutaka Kiyohara, Yusaku Nakabeppu, Toru Iwaki, Down-regulation of MET in hippocampal neurons of Alzheimer's disease brains, Neuropathology, 34, 3, 2014.06.
14. Mizuki Ohno, Kunihiko Sakumi, Ryutaro Fukumura, Masato Furuichi, Yuki Iwasaki, Masaaki Hokama, Toshimichi Ikemura, Teruhisa Tsuzuki, Yoichi Gondo, Yusaku Nakabeppu, 8-oxoguanine causes spontaneous de novo germline mutations in mice, Sci Rep, 4, 2014.04.
15. Hideo Tsuji, Hiroko Ishii-Ohba, Tadahiro Shiomi, Naoko Shiomi, Takanori Katsube, Masahiko Mori, Mitsuru Nenoi, Ohno Mizuki, Daisuke Yoshimura, Sugako OKa, Yusaku Nakabeppu, Kouichi Tasumi, Masahiro Muto, Toshikiko Sada, Nature of nontargeted radiation effects observed during fractionated irradiation-induced thymic lymphomagenesis in mice, J Radiat Res, 54, 3, 453-466, PMID: 23297316, 2013.05.
16. Noriko Yutsudo, Takkashi Kamada, Kosuke Kajitani, Hiroko Nomaru, Atsuhisa Katogi, Yoko H Ohnishi, Yoshinori N Ohnisi, Kei-ichiro Takase, Hiroshu Shugeto, SAKUMI Kunihiko, Yusaku Nakabeppu, fosB-null mice display impaired adult hippocampal neurogenesis and spontaneous epilepsy with depressive behavior, Neuropsychopharmacology, 38, 5, 2013.04.
17. Harini Sampath, Vladimir Vartanian, M. Rick Rollins, Kunihiko Sakumi, Yusaku Nakabeppu, R. Stephen Lloyd, 8-Oxoguanine DNA Glycosylase (OGG1) Deficiency Increases Susceptibility to Obesity and Metabolic Dysfunction, PLoS ONE, 7, 12, e51697, 2012.12.
18. Zijing Sheng, Sugako Oka, Daisuke Tsuchimoto, Abolhassani Nona, Nomaru Hiroko, Kunihiko Sakumi, Yamada Hidetaka, Yusaku Nakabeppu, 8-Oxoguanine causes neurodegeneration during MUTYH-mediated DNA base excision repair, J Clin Invest, 122, 12, 4344-4361, 2012.12.
19. Murakami Y, Ikeda Y, Yoshida N, Notomi S, Hisatomi T, Oka S, De Luca G, Yonemitsu Y, Bignami M, Nakabeppu Y, Ishibashi T., MutT Homolog-1 Attenuates Oxidative DNA Damage and Delays Photoreceptor Cell Death in Inherited Retinal Degeneration, Am J Pathol, 181, 4, 1378-1386, 2012.10.
20. Ohnishi YN, Ohnishi YH, Hokama M, Nomaru H, Yamazaki K, Tominaga Y, Sakumi K, Nestler EJ, Nakabeppu Y, FosB is essential for the enhancement of stress tolerance and antagonizes locomotor sensitization by ΔFosB, Biological Psychiatry, 186, 4, 1943-1950, 2011.09.
21. Iwama E, Tsuchimoto D, Iyama T, Sakumi K, Nakagawara A, Takayama K, Nakanishi Y, Nakabeppu Y., Cancer-Related PRUNE2 Protein Is Associated with Nucleotides and Is Highly Expressed in Mature Nerve Tissues, J Mol Neurosci, 44, 2, 2011.06.
22. Iyama T, Abolhassani N, Tsuchimoto D, Nonaka M, Nakabeppu Y., NUDT16 is a (deoxy)inosine diphosphatase, and its deficiency induces accumulation of single-strand breaks in nuclear DNA and growth arrest, Nucleic Acids Research, 38, 14, 4834-4843, 2010.06.
23. Abolhassani, N, Iyama, T, Tsuchimoto, D, Sakumi, K, Ohno, M, Behmanesh, M, Nakabeppu, Y., NUDT16 and ITPA play a dual protective role in maintaining chromosome stability and cell growth by eliminating dIDP/IDP and dITP/ITP from nucleotide pools in mammals, Nucleic Acids Research, 38, 9, 2891-2903, 2010.05.
24. Martin SA, McCabe N, Mullarkey M, Cummins R, Burgess DJ, Nakabeppu Y, Oka S, Kay E, Lord CJ, Ashworth A. , DNA polymerases as potential therapeutic targets for cancers deficient in the DNA mismatch repair proteins MSH2 or MLH1, Cancer Cell, 17, 3, 1235-1248, 2010.03.
25. Behmanesh, M., Sakumi, K., Abolhassani, N., Toyokuni, S., Oka, S., Ohnishi, Y., Tsuchimoto, D., and Nakabeppu, Y. , ITPase-deficient mice show growth retardation and die before weaning, Cell Death Differ, 16, 10, 1315-1322, 2009.10.
26. Kyota Fujita, Toshihiro Seike, Noriko Yutsudo, Mizuki Ohno, Hidetaka Yamada, Hiroo Yamaguchi, Kunihiko Sakumi, Yukiko Yamakawa, Mizuho A. Kido, Atsushi Takaki, Toshihiko Katafuchi, Yoshinori Tanaka, Yusaku Nakabeppu, Mami Noda , Hydrogen in Drinking Water Reduces Dopaminergic Neuronal Loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Mouse Model of Parkinson’s Disease, PLoS ONE, 4, 9, e7247, 2009.09.
27. Kajitani, K., Nomaru, H., Ifuku, M., Yutsudo, N., Dan, Y., Miura, T., Tsuchimoto, D., Sakumi, K., Kadoya, T., Horie, H., Poirier, F., Noda, M. and Nakabeppu, Y., Galectin-1 promotes basal and kainate-induced proliferation of neural progenitors in the dentate gyrus of adult mouse hippocampus, Cell Death Differ, 16, 3, 417-427, 2009.03.
28. Nonaka, M., Tsuchimoto, D., Sakumi, K. and Nakabeppu, Y., Mouse RS21-C6 is a mammalian 2’-deoxycytidine 5’-triphosphate pyrophosphohydrolase, preferring 5-iodocytosine, FEBS J, 276, 6, 1654-1666, 2009.03.
29. Nakane, H., Hirota, S., Brooks, P. J., Nakabeppu, Y., Nakatsu, Y., Nishimune, Y., Iino, A., and Tanaka, K. , Impaired spermatogenesis and elevated spontaneous tumorigenesis in xeroderma pigmentosum group A gene (Xpa)-deficient mice. , DNA Repair, 7, 12, 1938-1950, 2008.12.
30. Ohnishi YN, Sakumi K, Yamazaki K, Ohnishi YH, Miura T, Tominaga Y, Nakabeppu Y., Antagonistic regulation of cell-matrix adhesion by FosB and ΔFosB/Δ2ΔFosB encoded by alternatively spliced forms of fosB transcripts., Mol Biol Cell, 19(11): 4717-4729, 2008.11.
31. Dan Y, Ohta Y, Tsuchimoto D, Ohno M, Ide Y, Sami M, Kanda T, Sakumi K, Nakabeppu Y., Altered gene expression profiles and higher frequency of spontaneous DNA strand breaks in APEX2-null thymus., DNA Repair, 7 (9): 1437-1454, 2008.09.
32. Yanaru-Fujisawa R, Matsumoto T, Ushijima Y, Esaki M, Hirahashi M, Gushima M, Yao T, Nakabeppu Y, Iida M., Genomic and functional analyses of MUTYH in Japanese patients with adenomatous polyposis., Clin Genet, 73(6):545-553, 2008.06.
33. Ichikawa J, Tsuchimoto D, Oka S, Ohno M, Furuichi M, Sakumi K, Nakabeppu Y., Oxidation of mitochondrial deoxynucleotide pools by exposure to sodium nitroprusside induces cell death., DNA Repair, 7(3):418-430, 2008.03.
34. Oka S, Ohno M, Tsuchimoto D, Sakumi K, Furuichi M, Nakabeppu Y., Two distinct pathways of cell death triggered by oxidative damage to nuclear and mitochondrial DNAs., EMBO Journal., 27(2):421-432., 2008.01.
35. Sakamoto K, Tominaga Y, Yamauchi K, Nakatsu Y, Sakumi K, Yoshiyama K, Egashira A, Kura S, Yao T, Tsuneyoshi M, Maki H, Nakabeppu Y, Tsuzuki T., MUTYH-null mice are susceptible to spontaneous and oxidative stress induced intestinal tumorigenesis., Cancer Research, 67(14):6599-6604. , 2007.07.
36. Kuraoka I, Suzuki K, Ito S, Hayashida M, Kwei JS, Ikegami T, Handa H, Nakabeppu Y, Tanaka K., RNA polymerase II bypasses 8-oxoguanine in the presence of transcription elongation factor TFIIS., DNA Repair, 6, 6, 841-851, 2007.06.
37. Ohtsubo T, Ohya Y, Nakamura Y, Kansui Y, Furuichi M, Matsumura K, Fujii K, Iida M, Nakabeppu Y., Accumulation of 8-oxo-deoxyguanosine in cardiovascular tissues with the development of hypertension., DNA Repair, 6, 6, 760-769, 2007.06.
38. Nakamura T, Kitaguchi Y, Miyazawa M, Kamiya H, Toma S, Ikemizu S, Shirakawa M, Nakabeppu Y, Yamagata Y., Crystallization and preliminary X-ray analysis of human MTH1 complexed with two oxidized nucleotides, 8-oxo-dGMP and 2-oxo-dATP., Acta Crystallograph Sect F Struct Biol Cryst Commun., 62(Pt 12):1283-1285, 2006.12.
39. Kamiya H, Cadena-Amaro C, Dugue L, Yakushiji H, Minakawa N, Matsuda A, Pochet S, Nakabeppu Y, Harashima H., Recognition of Nucleotide Analogs Containing the 7,8-Dihydro-8-oxo Structure by the Human MTH1 Protein., J. Biochem., 140(6):843-849, 2006.12.
40. Akatsuka S, Aung TT, Dutta KK, Jiang L, Lee WH, Liu YT, Onuki J, Shirase T, Yamasaki K, Ochi H, Naito Y, Yoshikawa T, Kasai H, Tominaga Y, Sakumi K, Nakabeppu Y, Kawai Y, Uchida K, Yamasaki A, Tsuruyama T, Yamada Y, Toyokuni S., Contrasting genome-wide distribution of 8-hydroxyguanine and acrolein-modified adenine during oxidative stress-induced renal carcinogenesis., Am. J. Pathol., 169(4):1328-1342, 2006.10.
41. Arai T, Fukae J, Hatano T, Kubo S, Ohtsubo T, Nakabeppu Y, Mori H, Mizuno Y, Hattori N., Up-regulation of hMUTYH, a DNA repair enzyme, in the mitochondria of substantia nigra in Parkinson's disease., Acta Neuropathol, 112(2):139-145., 2006.08.
42. Sakai Y, Oda H, Yoshimura D, Furuichi M, Kang D, Iwai S, Hara T, Nakabeppu Y., The GT to GC single nucleotide polymorphism at the beginning of an alternative exon 2C of human MTH1 gene confers an amino terminal extension that functions as a mitochondrial targeting signal., J. Mol. Med., 4(8):660-670, 2006.08.
43. Arima, H., Kiyohara Y., Tanizaki Y., Nakabeppu Y., Kubo M., Kato I., Sueishi K., Tsuneyoshi M., Fujishima M. and Iida M, Angiotensin I-converting enzyme gene polymorphism modifies the smoking-cancer association: the Hisayama Study., Europ. J. Cancer Prev., 5(3):196-201, 2006.06.
44. Ohno M, Miura T, Furuichi M, Tominaga Y, Tsuchimoto D, Sakumi K, Nakabeppu Y., A genome-wide distribution of 8-oxoguanine correlates with the preferred regions for recombination and single nucleotide polymorphism in the human genome., Genome Res., 6(5):567-575, 2006.05.
45. Yamaguchi, H., Kajitani K., Dan Y., Furuichi M., Ohno M., Sakumi K., Kang D. and Nakabeppu Y., MTH1, an oxidized purine nucleoside triphosphatase, protects the dopamine neurons from oxidative damage in nucleic acids caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine., Cell Death Differ, 13(4):551-563, 2006.04.
46. Kajitani, K., Yamaguchi H., Dan Y., Furuichi M., Kang D. and Nakabeppu Y., MTH1, an oxidized purine nucleoside triphosphatase, suppresses the accumulation of oxidative damage of nucleic acids in the hippocampal microglia during kainate-induced excitotoxicity., J. Neurosci., 26(6):1688-1698, 2006.02.
47. Torisu, K., Tsuchimoto D., Ohnishi Y. and Nakabeppu Y., Hematopoietic tissue-specific expression of mouse Neil3 for endonuclease VIII-like protein., J. Biochem., 138, 6, 138(6):763-772, 2005.12.
48. Kurushima, H., Ohno M., Miura T., Nakamura T. Y., Horie H., Kadoya T., Ooboshi H., Kitazono T., Ibayashi S., Iida M. and Nakabeppu Y., Selective induction of ΔFosB in the brain after transient forebrain ischemia accompanied by an increased expression of galectin-1, and the implication of ΔFosB and galectin-1 in neuroprotection and neurogenesis., Cell Death Differ, 12, 8, 12 (8):1078-1096., 2005.08.
49. Kunisada, M., Sakumi K., Tominaga Y., Budiyanto A., Ueda M., Ichihashi M., Nakabeppu Y. and Nishigori C., 8-Oxoguanine Formation Induced by Chronic UVB Exposure Makes Ogg1 Knockout Mice Susceptible to Skin Carcinogenesis., Cancer Res, 65, 14, 65 (14):6006-10., 2005.07.
50. Campalans, A., Marsin S., Nakabeppu Y., O'Connor T R., Boiteux S. and Radicella J. P., XRCC1 interactions with multiple DNA glycosylases: A model for its recruitment to base excision repair., DNA Repair, 4, 7, 4 (7):826-35., 2005.07.
51. Fukae, J., Takanashi M., Kubo S.-i., Nishioka K.-i., Nakabeppu Y., Mori H., Mizuno Y. and Hattori N., Expression of 8-oxoguanine DNA glycosylase (OGG1) in Parkinson's disease and related neurodegenerative disorders., Acta Neurophathologica, 109, 3, 109 (3):256-262., 2005.03.
52. Behmanesh, M., Sakumi K., Tsuchimoto D., Torisu K., Ohnishi-Honda Y., Derrick E R. and Nakabeppu Y., Characterization of the structure and expression of mouse Itpa gene and its related sequences in the mouse genome., DNA Research, 12, 1, 12 (1):29-41., 2005.02.
53. Ushijima, Y., Y. Tominaga, T. Miura, Daisuke Tsuchimoto, K. Sakumi, and Y. Nakabeppu., A functional analysis of the DNA glycosylase activity of mouse MUTYH protein excising 2-hydroxyadenine opposite guanine in DNA., Nucleic Acids Res., 33, 2, 33(2):672-682., 2005.01.
54. Robertson, G. S., C. J. Lee, K. Sridhar, Y. Nakabeppu, M. Cheng, Y.-M. Wang, and M. G. Caron., Clozapine-, but not haloperidol-, induced increases in deltaFosB-like immunoreactivity is completely blocked in the striatum of mice lacking D3 dopamine receptors, Eur. J. Neurosci., 20, 11, 20(11):3189-3194., 2004.12.
55. Keiji Hashimoto, Yusaku Nakabeppu, Masaaki Moriya, Futile short-patch DNA base excision repair of adenine:8-oxoguanine mispair, Nucleic Acids Res., 32, 19, 32(19):5928-5234, 2004.11.
56. T. Miura, M. Takahashi, H. Horie, H. Kurushima, D. Tsuchimoto, K. Sakumi, Y. Nakabeppu, Galectin-1beta, a natural monomeric form of galectin-1 lacking its six amino-terminal residues promotes axonal regeneration but not cell death., Cell Death and Differentiation, 11, 10, 11(10):1076-1083, 2004.10.
57. Masaki Mishima, Yasunari Sakai, Noriyuki Itoh, Hiroyuki Kamiya, Masato Furuichi, Masayuki Takahashi, Yuriko Yamagata, Shigenori Iwai, Yusaku Nakabeppu, Masahiro Shirakawa, Structure of human MTH1, a Nudix family hydrolase that selectively degrades oxidized purine nucleoside triphosphates., J. Biol. Chem., 279, 32, 279(32):33806-33815, 2004.08.
58. Yohei Tominaga, Yasuhiro Ushijima, Daisuke Tsuchimoto, Masaki Mishima, Masahiro Shirakawa, Seiki Hirano, Kunihiko Sakumi, Yusaku Nakabeppu., MUTYH prevents OGG1 or APEX1 from inappropriately processing its substrate or reaction product with its C-terminal domain., Nucleic Acids Res., 32, 10, 32 (10):3198-3211, 2004.06.
59. Kimura, Y., S. Oda, A. Egashira, Y. Kakeji, H. Baba, Y. Nakabeppu, and Y. Maehara., A variant form of hMTH1, a human homologue of mutT E. coli mutator gene, correlates with somatic mutation in p53 tumour suppressor gene in gastric cancer patients., J. Med. Genet., 41, 5, 41 (5): e57, 2004.05.
60. Iida, T., Furuta, A., Nakabeppu, Y., and Iwaki, T., Defense mechanism to oxidative DNA damage in glial cells., Neuropathol., 24, 2, 24 (2): 125-130, 2004.05.
61. Kamiya, H., H. Yakushiji, L. Dugue, M. Tanimoto, S. Pochet, Y. Nakabeppu, H. Harashima., Probing the substrate recognition mechanism of the human MTH1 protein by nucleotide analogs., J. Mol. Biol., 336, 4, 336 (4): 843-850, 2004.02.
62. Ichinoe, A., M. Behmanesh, Y. Tominaga, Y. Ushijima, S. Hirano, Y. Sakai, D. Tsuchimoto, K. Sakumi, N. Wake, Y. Nakabeppu., Identification and characterization of two forms of mouse MUTYH proteins encoded by alternatively spliced transcripts., Nucleic Acids Res., 32, 2, 32(2):477-487, 2004.01.
63. Russo, M. T., M. F. Blasi, F. Chiera, P. Fortini, P. Degan, P. Macpherson, M. Furuichi, Y. Nakabeppu, P. Karran, G. Aquilina, and M. Bignami., The oxidized Deoxynucleotide Triphosphate Pool is a Significant Contributor to Genetic Instability in Mismatch Repair-Deficient Cells., Mol. Cell Biol., 24, 1, 24: 465-474., 2004.01.
64. Xu, P., K. Yoshioka, D. Yoshimura, Y. Tominaga, T. Nishioka, M. Ito, and Y. Nakabeppu., In vitro development of mouse embryonic stem cells lacking JSAP1 scaffold protein revealed its requirement during early embryonic neurogenesis., J. Biol. Chem., 278, 48, 278:48422-48433, 2003.11.
65. Hirano, S., Y. Tominaga, A. Ichinoe, Y. Ushijima, D. Tsuchimoto, Y. Honda-Ohnishi, T. Ohtsubo, K. Sakumi, and Y. Nakabeppu., Mutator phenotype of MUTYH-null mouse embryonic stem cells., J. Biol. Chem., 278, 40, 278:38121-38124, 2003.10.
66. Yoshimura, D., K. Sakumi, M. Ohno, Y. Sakai, M. Furuichi, S. Iwai, and Y. Nakabeppu., An oxidized purine nucleoside triphosphatase, MTH1 suppresses cell death caused by oxidative stress., J. Biol. Chem., 278:37965-37973, 2003.09.
67. Tahara, K., D. Tsuchimoto, Y. Tominaga, S. Asoh, S. Ohta, M. Kitagawa, H. Horie, T. Kadoya, and Y. Nakabeppu., ΔFosB but not FosB Induces Delayed Apoptosis Independent of Cell Proliferation in the Rat1a Embryo Cell Line., Cell Death Diff., 10, 5, 10:496-507, 2003.04.
68. Yamazaki, K., T. Aso, Y. Ohnishi, M. Ohno, K. Tamura, T. Shuin, S. Kitajima, and Y. Nakabeppu., Mammalian elongin A is not essential for cell viability but required for proper cell-cycle progression with limited alteration of gene expression., J. Biol. Chem., 278, 15, 278:13585-13589, 2003.04.
69. Sakumi, K., Y. Tominaga, M. Furuichi, P. Xu, T. Tsuzuki, M. Sekiguchi, and Y. Nakabeppu., Ogg1 Knockout-associated Lung Tumorigenesis and Its Suppression by Mth1 Gene Disruption., Cancer Res., 63, 5, 63:902-905, 2003.03.
70. Tsuruya, K., M. Furuichi, Y. Tominaga, M. Shinozaki, M. Tokumoto, T. Yoshimitsu, K. Fukuda, H. Kanai, H. Hirakata, M. Iida, and Y. Nakabeppu., Accumulation of 8-oxoguanine in the cellular DNA and the alteration of the OGG1 expression during ischemia-reperfusion injury in the rat kidney., DNA Repair, 2, 2, 2:211-229, 2003.02.
71. Ide, Y., D. Tsuchimoto, Y. Tominaga, Y. Iwamoto, and Y. Nakabeppu., Characterization of the genomic structure and expression of the mouse Apex2 gene., Genomics, 81, 1, 81:47-57, 2003.01.
72. Takahashi, M., F. Maraboeuf, Y. Sakai, H. Yakushiji, M. Mishima, M. Shirakawa, S. Iwai, H. Hayakawa, M. Sekiguchi, and Y. Nakabeppu., Role of tryptophan residues in the recognition of mutagenic oxidized nucleotides by human antimutator MTH1 protein., J. Mol. Biol., 319, 1, 319:129-139, 2002.05.
73. Nishioka, T., K. Sakumi, T. Miura, K. Tahara, H. Horie, T. Kadoya, and Y. Nakabeppu., fosB gene products trigger cell proliferation and morphological alteration with an increased expression of a novel processed form of galectin-1 in the rat 3Y1 embryo cell line., J. Biochem., 131, 5, 131:653-661, 2002.05.
74. Kikuchi, H., A. Furuta, K. Nishioka, S. O. Suzuki, Y. Nakabeppu, and T. Iwaki., Impairment of mitochondrial DNA repair enzymes against accumulation of 8-oxo-guanine in the spinal motor neurons of amyotrophic lateral sclerosis., Acta Neuropathol., 103, 4, 103:408-414, 2002.04.
75. Sakai, Y., M. Furuichi, M. Takahashi, M. Mishima, S. Iwai, M. Shirakawa, and Y. Nakabeppu., A molecular basis for the selective recognition of 2-hydroxy-dATP and 8-Oxo-dGTP by human MTH1., J. Biol. Chem., 277, 10, 277:8579-8587, 2002.03.
76. Hayashi, H., Y. Tominaga, S. Hirano, A. E. McKenna, Y. Nakabeppu, and Y. Matsumoto., Replication-Associated Repair of Adenine:8-Oxoguanine Mispairs by MYH., Current Biol., 12, 4, 12:335-339, 2002.02.
77. Fujikawa, K., H. Yakushiji, Y. Nakabeppu, T. Suzuki, M. Masuda, H. Ohshima, and H. Kasai., 8-Chloro-dGTP, a hypochlorous acid-modified nucleotide, is hydrolyzed by hMTH1, the human MutT homolog., FEBS Lett., 512, 1-3, 512:149-151, 2002.02.
78. Iida, T., A. Furuta, K. Nishioka, Y. Nakabeppu, and T. Iwaki., Expression of 8-oxoguanine DNA glycosylase is reduced and associated with neurofibrillary tangles in Alzheimer's disease brain., Acta Neuropathol., 103, 1, 103:20-25, 2002.01.
79. Tsuzuki, T., A. Egashira, H. Igarashi, T. Iwakuma, Y. Nakatsuru, Y. Tominaga, H. Kawate, K. Nakao, K. Nakamura, F. Ide, S. Kura, Y. Nakabeppu, M. Katsuki, T. Ishikawa, and M. Sekiguchi., Spontaneous tumorigenesis in mice defective in the MTH1 gene encoding 8-oxo-dGTPase., Proc. Natl. Acad. Sci. U. S. A., 98, 20, 98:11456-11461, 2001.09.
80. Furuta, A., T. Iida, Y. Nakabeppu, and T. Iwaki., Expression of hMTH1 in the hippocampi of control and Alzheimer's disease., Neuroreport, 12, 13, 12:2895-2899, 2001.09.
81. Jaiswal, M., N. F. LaRusso, K. Nishioka, Y. Nakabeppu, and G. J. Gores., Human Ogg1, a protein involved in the repair of 8-oxoguanine, is inhibited by nitric oxide., Cancer Res., 61, 17, 61:6388-6393, 2001.09.
82. Kasprzak, K. S., Y. Nakabeppu, T. Kakuma, Y. Sakai, K. Tsuruya, M. Sekiguchi, J. M. Ward, B. A. Diwan, K. Nagashima, and B. H. Kasprzak., Intracellular Distribution of the Antimutagenic Enzyme MTH1 in the Liver, Kidney, and Testis of F344 Rats and its Modulation by Cadmium., Exp. Toxico. Pathol., 53, 5, 53:325-336, 2001.07.
83. Tsuchimoto, D., Y. Sakai, K. Sakumi, K. Nishioka, M. Sasaki, T. Fujiwara, and Y. Nakabeppu., Human APE2 protein is mostly localized in the nuclei and to some extent in the mitochondria, while nuclear APE2 is partly associated with proliferating cell nuclear antigen., Nucleic Acids Res., 29, 11, 29:2349-2360., 2001.06.
84. Iida, T., A. Furuta, M. Kawashima, J. Nishida, Y. Nakabeppu, and T. Iwaki., Accumulation of 8-oxo-2'-deoxyguanosine and increased expression of hMTH1 protein in brain tumors., Neuro-oncol., 3, 2, 3:73-81, 2001.04.
85. Rodriguez, J. J., D. R. Garcia, Y. Nakabeppu, and V. M. Pickel., Enhancement of laminar FosB expression in frontal cortex of rats receiving long chronic clozapine administration., Exp. Neurol., 168, 2, 168:392-401, 2001.04.
86. Rodriguez, J. J., D. R. Garcia, Y. Nakabeppu, and V. M. Pickel., FosB in rat striatum: normal regional distribution and enhanced expression after 6-month haloperidol administration., Synapse, 39, 2, 39:122-132, 2001.02.
87. Fujikawa, K., H. Kamiya, H. Yakushiji, Y. Nakabeppu, and H. Kasai., Human MTH1 protein hydrolyzes the oxidized ribonucleotide, 2-hydroxy-ATP., Nucleic Acids Res., 29, 2, 29:449-454., 2001.01.
88. Shimokawa, H., Y. Fujii, M. Furuichi, M. Sekiguchi, and Y. Nakabeppu., Functional significance of conserved residues in the phosphohydrolase module of Escherichia coli MutT protein., Nucleic Acids Res., 28, 17, 28:3240-3249, 2000.09.
89. Miyako, K., C. Takamatsu, S. Umeda, T. Tajiri, M. Furuichi, Y. Nakabeppu, M. Sekiguchi, N. Hamasaki, K. Takeshige, and D. Kang., Accumulation of adenine DNA glycosylase-sensitive sites in human mitochondrial DNA., J. Biol. Chem., 275, 16, 275:12326-12330, 2000.04.
90. Fujii, Y., H. Shimokawa, M. Sekiguchi, and Y. Nakabeppu., Functional significance of the conserved residues for the 23-residue module among MTH1 and MutT family proteins., J. Biol. Chem., 274, 53, 274:38251-38259, 1999.12.
91. Shimura-Miura, H., N. Hattori, D. Kang, K. Miyako, Y. Nakabeppu, and Y. Mizuno., Increased 8-oxo-dGTPase in the mitochondria of substantia nigral neurons in Parkinson's disease., Ann. Neurol., 46, 6, 46:920-924, 1999.11.
92. Oda, H., A. Taketomi, R. Maruyama, R. Itoh, K. Nishioka, H. Yakushiji, T. Suzuki, M. Sekiguchi, and Y. Nakabeppu., Multi-forms of human MTH1 polypeptides produced by alternative translation initiation and single nucleotide polymorphism., Nucleic Acids Res., 27, 22, 27:4335-4343, 1999.11.
93. Fujikawa, K., H. Kamiya, H. Yakushiji, Y. Fujii, Y. Nakabeppu, and H. Kasai., The oxidized forms of dATP are substrates for the human MutT homologue, the hMTH1 protein., J. Biol. Chem., 274, 26, 274:18201-18205., 1999.06.
94. Nishioka, K., T. Ohtsubo, H. Oda, T. Fujiwara, D. Kang, K. Sugimachi, and Y. Nakabeppu., Expression and differential intracellular localization of two major forms of human 8-oxoguanine DNA glycosylase encoded by alternatively spliced OGG1 mRNAs., Mol. Biol. Cell, 10, 5, 10:1637-1652., 1999.05.
Presentations
1. Yusaku Nakabeppu, Oxidative DNA damage and repair in carcinogenesis and neurodegeneration, International Symposium on Immune Diversity and Cancer Therapy Kobe 2017, 2017.01.28.
2. Ohno Mizuki, Kunihiko Sakumi, Yusaku Nakabeppu, Regulation of base substitution mutagenesis and chromosome recombination induced by 8-oxoguanine accumulated in the genome, The 39th Annual Meeting of the Molecular Biology Society of Japan, 2016.12.02.
3. Guianfranco Mazzei, Erika Castillo, Kunihiko Sakumi, Takashi Saito, Takaomi Saido, Yusaku Nakabeppu, Impaired hippocampal neurogenesis in App-knock-in model mice of Alzheimer’s disease, The 39th Annual Meeting of the Molecular Biology Society of Japan, 2016.12.01.
4. Erika Castillo, Julio Leon, Nona Abolhassani, Guianfranco Mazzei, Kunihiko Sakumi, Takashi Saito, Takaomi Saido, Yusaku Nakabeppu, Comparative gene expression profiling of triple-transgenic 3xTg-AD and APP-knock-in model mice of Alzheimer’s disease, The 46th Annual Meeting of Society for Neuroscience, 2016.11.15.
5. Shunji Nakatake, Yusuke Murakami, Yasuhiso Ikeda, Kota Fujiwara, Takashi Tachibana, Toshio Hisatomi, Shigeo Yoshida, Tatsuro Ishibashi, Yusaku Nakabeppu, Koh -hei Sonoda, Oxidative DNA Damage in Microglia Exacerbates Retinal Inflammation and Degeneration through MUTYH-mediated Base Excision Repair in a Mouse Model of Retinitis Pigmentosa, ARVO 2016 Annual Meeting, 2016.05.02.
6. Sugako Oka, Nona Abolhassani, Julio Leon, Masaaki Hokama, Masahiro Shijo, Hideomi Hamasaki, Toru Iwaki, Yutaka Kiyohara, Tomomi Ide, Dongchon Kang, Yusaku Nakabeppu, Molecular pathophysiology of insulin depletion, mitochondrial dysfunction and oxidative stress in Alzheimer's disease brain, The 11th International Symposium on Geriatrics and Gerontology, 2016.02.06.
7. Nona Abolhassani, Masaaki Hokama, Daisuke Saitou, Mikita Suyama, Toru Iwaki, Yutaka Kiyohara, Yusaku Nakabeppu, Characterization of transcript variants expressed in Alzheimer’s disease brain with human transcriptome array and deep RNA sequencing analyses: The Hisayama Study, 2nd Zing Neurodegeneration Conference, 2015.12.03.
8. Julio Leon, Kunihiko Sakumi, Sugako Oka, Erika Castillo, Yusaku Nakabeppu, 8-Oxoguanine accumulated in mitochondrial DNA disturbs neuritic regeneration of cultured adult mouse cortical neurons under conditions of oxidative stress, 45th Annual Meeting of Society for Neuroscience, 2015.10.17.
9. Shunji Nakatake, Yusuke Murakami, Yasuhiro Ikeda, Noriko Yoshida, Takashi Tachibana, Toshio Hisatomi, Yusaku Nakabeppu, Tatsuro Ishibashi, MUTYH, a Base Excision Repair Enzyme against Oxidative DNA Damage, Induces Single-strand Break Formation and Mediates Photoreceptor Cell Death in a Mouse Model of Retinitis Pigmentosa, The 8th Joint Meeting of Japan-China-Korea Ophthalmologists, 2015.10.17.
10. Mizuki Ohno, Noriko Takano, Kunihiko Sakumi, Ryutaro Fukumura, Yuki Iwasaki, Toshimichi Ikemura, Yoichi Gondo, Yusaku Nakabeppu, Yoshimichi Nakatsu, Teruhisa Tsuzuki, The role of MUTYH in the oxidative stress-induced mutagenesis and tumorigenesis in the mouse intestine, The Zing conference on “Genomic Integrity", 2015.08.04.
11. Nona Abolhassani, Masaaki Hokama, Daisuke Saitou, Mikita Suyama, Toru Iwaki, Yutaka Kiyohara, Yusaku Nakabeppu, Characterization of transcript variants expressed in Alzheimer´s disease brains with human transcriptome array and deep RNA sequencing analyses: The Hisayama Study, The 38th Annual Meeting of the Japan Neuroscience Society, 2015.07.30.
12. Julio Jesus Leon Incio, Kunihiko Sakumi, Sugako Oka, Erika Castillo, Yusaku Nakabeppu, Cortical neurons isolated from adult Mth1/Ogg1-double-knockout mouse exhibit impaired neurite regeneration under conditions of oxidative stress, The 38th Annual Meeting of the Japan Neuroscience Society, 2015.07.30.
13. Atsuhisa Katogi, Hiroko Nomaru, Yoshinori N. Ohnishi, Kunihiko Sakumi, Yusaku Nakabeppu, Characterization of Fosb gene products expressed in various Fosb mutant mice, The 38th Annual Meeting of the Japan Neuroscience Society, 2015.07.30.
14. Kosuke Kajitani, Yusaku Nakabeppu, Yoshihiko Kadoya, Hidenori Horie, Characterization of galectin-1-positive cells in the mouse hippocampus: the relevance of galectin-1 to interneurons, The 38th Annual Meeting of the Japan Neuroscience Society, 2015.07.30.
15. Zijing Sheng, Yusaku Nakabeppu, Cranial irradiation causes hippocampal degeneration through accumulation of 8-oxoguanine in mitochondrial DNA in neurons, The 38th Annual Meeting of the Japan Neuroscience Society, 2015.07.30.
16. Sugako Oka, Julio Leon, Nona Abolhassani, Masaaki Hokama, Toru Iwaki, Yutaka Kiyohara, Dongchon Kang, Yusaku Nakabeppu, Interspecies comparative gene expression profiling revealed impaired insulin production and insulin signaling in Alzheimer's disease brains: The Hisayama Study , The 2015 Alzheimer's Disease Congress, 2015.06.25.
17. Yusaku Nakabeppu, Oxidation of nucleic acids and control mechanisms of spontaneous mutagenesis and tumorigenesis in mammals, The CRUK/MRC Oxford Institute for Radiation Oncology 2015 Seminar Series , 2015.06.23.
18. Yusaku Nakabeppu, Sugako Oka, Zijing Sheng, Kunihiko Sakumi, MUTYH-dependent programmed cell death triggered by 8-oxoguanine and its implication in tumor suppression and neurodegeneration, 15th International Congress of Radition Research: ICRR2015, 2015.05.27.
19. Sugako Oka, Ohno Mizuki, Daisuke Tsuchimoto, Kunihiko Sakumi, Yusaku Nakabeppu, Two distinct pathways of cell death triggered by oxidative damage to nuclear and mitochondrial DNAs, BIT’8th, Annual World Cancer Congress-2015, 2015.05.17.
20. Shunji Nakatake, Yusuke Murakami, Yasuhiro Ikeda, Noriko Yoshida, Takashi Tachibana, Toshio Hisatomi, Yusaku Nakabeppu, Tatsuro Ishibashi, MUTYH, a Base Excision Repair Enzyme against Oxidative DNA Damage, Induces Single-strand Break Formation and Mediates Photoreceptor Cell Death in a Mouse Model of Retinitis Pigmentosa, The Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) 2015, 2015.05.07.
21. Sugako Oka, Julio Leon, Nona Abolhassani, Masaaki Hokama, Toru Iwaki, Yutaka Kiyohara, Dongchon Kang, Yusaku Nakabeppu, Interspecies comparative gene expression profiling revealed impaired insulin production and insulin signaling accompanied by mitochondrial dysfunction in Alzheimer's disease brains: The Hisayama Study, 第88回薬理学会年会, 2015.03.20.
22. Sugako Oka, Julio Leon, Masaaki Hokama, Toru Iwaki, Yutaka Kiyohara, Dongchon Kang, Yusaku Nakabeppu, Impaired insulin production/signaling accompanied by mitochondrial dysfunction and oxidative stress in Alzheimer's disease brains, Progress 100: Kyushu-U and Stanford-U Joint Research and Education Program:First Symposium: From Genes to Human Diseases, 2015.03.17.
23. Yusaku Nakabeppu, Sugako Oka, Julio Leon, Nona Abolhassani, Masaaki Hokama, Toru Iwaki, Yutaka Kiyohara, Dongchon Kang, Impaired insulin production and insulin signaling accompanied by mitochondrial dysfunction in Alzheimer's disease brains: The Hisayama Study, 包括型脳科学研究推進支援ネットワーク 冬のシンポジウム, 2014.12.11.
24. Nona Abolhassani, Massaki Hokama, Toru Iwaki, Yutaka Kiyohara, Yusaku Nakabeppu, Characterization of transcript variants expressed in Alzheimer’s disease brains with human transcriptome array and deep RNA sequencing analyses: The Hisayama Study, 第37回日本分子生物学会年会, 2014.11.26.
25. Yusaku Nakabeppu, Mizuki Ohno, Sugako Oka, Zijing Sheng, Kunihiko Sakumi, Control mechanisms of genetic diversity and programed cell death induced by 8-oxoguanine in mammals, 9th 3R (Replication, Repair, recombination) symposium, 2014.11.18.
26. Michel J. Massaad, Daisuke Tsuchimoto, Janet Chou, Toshiro Ohsumi, Jia Zhou, Haifa Jabara, Jennifer Kane, Klaus Schmitz, Markianos Kyriacos, Kumiko Torisu, Yusaku Nakabeppu, Peter Kang, Eliane Choueiry, Andre Megarbane, Masayuki Mizui, George Tsokos, Waleed El-Herz, Luigi Notarangelo, Susan Wallace, Raif S. Geha, THE HUMAN NEI ENDONUCLEASE VIII-LIKE 3 (NEIL3) IS A NOVEL GENE ASSOCIATED WITH THE DEVELOPMENT OF AUTO-ANTIBODIES , 16th Biennial Meeting of the European Society for Immunodeficiency, 2014.10.29.
27. Teruhisa Tsuzuki, Mizuki Ohno, Noriko Takano, Kenichi Taguchi, Yusaku Nakabeppu, Yasunobu Aoki, Takehiko Nohmi, Yoshimichi Nakatsu, Oxidative stress-induced intestinal tumors in Mutyh-deficient mice treated with low doses of potassium bromate, 5th US-Japan DNA Repair Meeting, 2014.10.29.
28. Yusaku Nakabeppu, Sugako Oka, Zijing Sheng, Kunihiko Sakumi, MUTYH-dependent programed cell death induced by 8-oxoguanine accumulated in cellular DNAs and its implication in tumorigenesis and neruodegeneration, 5th US-Japan DNA Repair Meeting, 2014.10.29.
29. Taikai Inoue, Akio Matsumoto, Megumi Yamafuji, Tomoko Tachibana, Yusaku Nakabeppu, Haruaki Nakaya, Mami Noda, Stomach-brain interaction induced by molecular hydrogen in Parkinson’s disease model animal , 第37回日本神経科学大会, 2014.09.13.
30. Hiroko Nomaru, Kunihiko Sakumi, Atsuhisa Katogi, Daisuke Tsuchimoto, Yusaku Nakabeppu, Fosb gene products contribute to excitotoxic microglial activation by regulating the expression of complement C5a receptors in microglia, 第37回日本神経科学大会, 2014.09.11.
31. Yusaku Nakabeppu, Mizuki Ohno, Ryutaro Fukumura, Yuki Iwasaki, Toshimichi Ikemura, Yoichi Gondo, Kunihiko Sakumi, Oxidation of nucleic acids and control mechanisms of genetic diversity in mammals, International Symposium on Germline Mutagenesis and Biodiversification, 2014.03.21.
32. Zijing Sheng, Sugako Oka, Yasuhiro Ikeda, Margherita Bignami, Yusaku nakabeppu, 8-oxo-dGTP generated in nucleotide pools is a major cause of neurodegeneration under oxidative stress, International symposium "New Frontier of Molecular Neuropathology 2014", 2014.03.17.
33. 大野 みずき, 作見 邦彦, 福村 龍太郎, 岩崎 裕貴, 池村 淑道, 續 輝久, 権藤 洋一, 中別府 雄作, 8-Oxoguanine causes spontaneous de novo germline mutations : a study from the mutator mouse line, SMBE Satellite Meeting / NIG International Symposium: The Causes of Genome Evolution, 2014.03.14.
34. Hiroko Nomaru, Kunihiko Sakumi, Atsuhisa Katogi, Yoshinori N Ohnishisi, Daisuke Tsuchimoto, Yusaku Nakabeppu, Microglial activation by Fosb Gene, International Symposium between Kyushu University Post-Global Centers of Excellence Program and School of Biomedical Sciences, Monash University, Melbourne, Australia, 2014.02.07.
35. Yasuto Yoneshima, Daisuke Tsuchimoto, Nona Abolhassani, Teruaki Iyama, Kunihiko SakumiI, Naoko Shiomi, Masahiko Mori, Tadahiro Shiomi, Yusaku Nakabeppu, Accumulation of deoxyinosine triphosphate induces mismatch repair-dependent cell growth arrest and instability of genomic DNA, International Symposium between Kyushu University Post-Global Centers of Excellence Program and School of Biomedical Sciences, Monash University, Melbourne, Australia, 2014.02.07.
36. 中別府 雄作, 大野 みずき, 作見 邦彦, Oxidation of nucleic acids by reactive oxygen species and control mechanisms of genetic diversity in mammals, International Symposium between Kyushu University Post-Global Centers of Excellence Program and School of Biomedical Sciences, Monash University, 2014.02.07.
37. Erika Castillo, Julio Leon, 秋本 頼子, 作見 邦彦, 岡 素雅子, 土本 大介, 中別府 雄作, Cytotoxic effects of X-ray irradiation on proliferating and differentiated human neuroblastoma cell line SH-SY5Y, and their modulation by BDNF and inhibitors for CDK5 and calpains, 第36回日本分子生物学会, 2013.12.04.
38. Hiroko Nomaru, Kunihiko Sakumi, Daisuke Tsuchimoto, Yusaku Nakabeppu, Fosb gene products regulate expression of C5ar1 and C5l2 genes and microglial activation, The 43rd annual meeting of the Society for Neuroscience, 2013.11.12.
39. Yuko Kobayakawa, Kunihiko Sakumi, Yusaku Nakabeppu, Dual effects of Galectin-1 in amyotrophic lateral screlosis, The 43rd annual meeting of the Society for Neuroscience, 2013.11.11.
40. Sugako Oka, Julio Leon, Masaaki Hokama, Atsuhisa Katogi, Kunihiko Sakumi, Dongchon Kang, Yusaku Nakabeppu, Expression of human mitochondrial transcriptional factor A (hTFAM) improves cognitive function in Alzheimer’s disease model mice, International Symposium on Mitochondria 2013(第13回日本ミトコンドリア学会), 2013.11.06.
41. Zijing Sheng, Sugako Oka, Yusaku Nakabeppu, MUTYH-dependent neurodegeneration initiated by mitochondrial accumulation of 8-oxoguanine in neurons is efficiently suppressed by MTH1 and OGG1., 10th Conference of the Asian Society of Mitochondrial Research and Medicine (ASMRM) , 2013.11.05.
42. Sugako Oka, Dongchon Kang, Yusaku Nakabeppu, Expression of human mitochondrial transcriptional factor A (hTFAM) improves cognitive function in Alzheimer’s disease model mice, 2013 Alzheimer's Association International Conference, 2013.07.16.
43. Yoriko Akimoto, Sugako Oka, Julio Leon, Yusaku Nakabeppu, Quantitative detection of oxidative DNA damage in brains of the triple transgenic Alzheimer’s disease mouse model, 2013 Alzheimer's Association International Conference, 2013.07.15.
44. Pathophysiology caused by oxidative modification of nucleic acids and protective mechanisms

For living organisms, the most fundamental biological function is maintaining the integrity of their genomic DNAs harboring the genetic information and transmitting them precisely from cell to cell, as well as from parents to their offspring. The genomic DNA and its precursor nucleotides, are always in danger of chemical modification by reactive molecules such as reactive oxygen (ROS) or nitrogen species (RNS), which are produced as byproducts during the oxygen respiration and other normal metabolisms or as true products for host defense or signal transduction. In DNA or nucleotide pools, various chemical modifications of bases and nucleotides such as oxidation, deamination and nitration are induced by the reactive molecules, and such modified nucleic acids may cause mutations or cell death if they are not repaired or eliminated. Mutations may induce cancers, and cell death may be related to various degenerative diseases. In mammals including human, mitochondrion also maintains its genomic DNA as does nucleus in which vast majority of genetic information is maintained as nuclear genome. Mitochondria produce energy essential for maintenance of life by oxygen respiration, however, superoxide anions are always generated through reduction of oxygens by electrons leaked from the electron transport chain. Because highly reactive molecules such as hydrogen peroxides, hydroxyl radicals or peroxynitrites are easily formed from superoxide anions, mitochondria are always exposed to oxidative stress.
While exploring cellular damage caused by chemical modification of nucleotides or DNA as well as protective mechanisms against such damage, we found that 8-oxoguanine (8-oxoG), a common DNA lesion caused by ROS, is associated with not only mutagenesis but also cell death, the former resulting in carcinogenesis, and the latter in tissue degeneration. 8-OxoG accumulated in either nuclear or mitochondrial DNA is recognized by a common sensor molecule, MUTYH once adenine is inserted opposite 8-oxoG during replication, and thus triggering two distinct programs of cell death through activation of various effector molecules, respectively. We recently demonstrated that the two distinct programs of cell death play crucial roles during striatal degeneration induced by 3-nitropropionic acid or retinitis pigmentosa in Pde6b mutant mice. In this symposium, I will present our recent studies on the pathophysiology caused by 8-oxoG accumulated in cellular genomes and protective mechanisms against the damage..
45. Hiroko Nomaru, Kunihiko Sakumi, Noriko Yutsudo, Daisuke Tsuchimoto, Yusaku Nakabeppu, Comprehensive analysis of gene expression regulated by Fosb gene in brain-derived cells, Neuro2013 Joint Conference of: The 36th annual Meeting of the Japan Neuroscience Society The 56th Annual Meeting of the Japanese Society for Neurochemistry The 23rd Annual Meeting of Japanese Neural Network Society, 2013.06.22.
46. Yuko Kobayakawa, Kunihiko Sakumi, Yusaku Nakabeppu, Dual effects of Galectin-1 in amyotrophic lateral sclerosis, Neuro2013 Joint Conference of: The 36th annual Meeting of the Japan Neuroscience Society The 56th Annual Meeting of the Japanese Society for Neurochemistry The 23rd Annual Meeting of Japanese Neural Network Society, 2013.06.22.
47. Zijing Sheng, Yusaku Nakabeppu, Expression of the defense enzymes MTH1, OGG1 and MUTYH against oxidative damage in nucleic acids in the mouse brain, Neuro2013 Joint Conference of: The 36th annual Meeting of the Japan Neuroscience Society The 56th Annual Meeting of the Japanese Society for Neurochemistry The 23rd Annual Meeting of Japanese Neural Network Society, 2013.06.22.
48. Yoriko Akimoto, Sugako Oka, Yusaku Nakabeppu, Quantitative detection of oxidative DNA damage in brains of the triple transgenic Alzheimer's disease mouse model, Neuro2013 Joint Conference of: The 36th annual Meeting of the Japan Neuroscience Society The 56th Annual Meeting of the Japanese Society for Neurochemistry The 23rd Annual Meeting of Japanese Neural Network Society, 2013.06.22.
49. Noriko Yutsudo, Takashi Kamada, Kosuke Kajitani, Hiroko Nomaru, Atsuhisa Katogi, Yoko H. Ohnishi, Yoshinori N. Ohnishi, Kei-ichiro Takase, SAKUMI Kunihiko, Hiroshi Shigeto, Yusaku Nakabeppu, fosB-null mice display impaired adult hippocampal neurogenesis and spontaneous epilepsy with depressive behavior, Neuro2013 Joint Conference of: The 36th annual Meeting of the Japan Neuroscience Society The 56th Annual Meeting of the Japanese Society for Neurochemistry The 23rd Annual Meeting of Japanese Neural Network Society, 2013.06.20.
50. Sugako Oka, Dongchon Kang, Yusaku Nakabeppu, Expression of human mitochondrial transcriptional factor A (hTFAM) improves cognitive function in Alzheimer's disease model mice, Neuro2013 Joint Conference of: The 36th annual Meeting of the Japan Neuroscience Society The 56th Annual Meeting of the Japanese Society for Neurochemistry The 23rd Annual Meeting of Japanese Neural Network Society, 2013.06.20.
51. Yusaku Nakabeppu, Quality Control of Nucleotide Pools is Essential for Cellular Homeostasis, Invited seminar at Institute of Molecular Cancer Research University of Zurich, Switzerland, 2013.04.19.
52. Zijing Sheng, Sugako Oka, Daisuke Tsuchimoto, Kunihiko Sakumi, Yusaku Nakabeppu, 8-Oxoguanine in brain causes complex neurodegeneration through DNA repair, Gordon research conference on Oxidative Stress & Disease, 2013.04.14.
53. Yusaku Nakabeppu, Zijing Sheng, Sugako Oka, Oxidative damage in brain genomes and neuroprotective mechanisms, 第90回日本生理学会大会, 2013.03.29.
54. Yusaku Nakabeppu, Quality Control of Nucleotide Pools is Essential for Cellular Homeostasis, Invited seminar at Istituto Superiore di Sanitá, Roma, Italy, 2013.03.12.
55. Genome DNA is constantly exposed to reactive oxygen species which are generated by extrinsic factors such as ionizing radiation or chemicals, and intrinsic factors such as cellular respiration. 8-Oxoguanine (8-oxoG) is known to be a major cause of spontaneous mutation because it can pair with not only cytosine but also adenine. Many organisms possess effective system to reduce 8-oxoG-induced mutation. In mouse, Mth1 hydrolyzes 8-oxo-dGTP to mono-phosphate form to prevent the incorporation of 8-oxo-dGTP during DNA replication. Ogg1, 8-oxoG DNA glycosylase, remove 8-oxoG in the genome to prevent accumulation of 8-oxoG. Mutyh remove adenine which incorporates opposite to 8-oxoG in template strand to prevent mispairing.
To elucidate the effect of 8-oxoG in the genome of somatic cell and germ cell, we established a triple knockout mouse line which lacks three genes, Ogg1, Mth1, Mutyh. The mutant mice exhibited a short life-span and early-onset carcinogenesis in multiple organs. We observed apparent increases in neonatal death with occasional congenital abnormalities such as spina bifida. We found hydrocephalus, microphthalmia, white spot and other abnormal phenotypes. The hydrocephalus and white spot were consistent with autosomal dominant transmission. These results suggest that the lacking three genes increase mutation rates not only in somatic cells but also germ cells. We will also present sequence data obtained from genomes of the mutant mouse line..
56. Eiko Ohta, Kunihiko Sakumi, Daisuke Tsuchimoto, Yuka Takiguchi, Yusaku Nakabeppu, 2-OH-ATP as a signal molecule for the oxidative stress in mammalian cells, The 8th 3R Symposium (International Symposium on DNA Replication, Recombination and Repair), 2012.11.27.
57. Yoriko Akimoto, Yusaku Nakabeppu, Identification and quantification of radiation-induced modified purine nucleosides, The 8th 3R Symposium (International Symposium on DNA Replication, Recombination and Repair), 2012.11.26.
58. Yusaku Nakabeppu, Quality control in the nucleotide pools is essential for cellular homeostasis, Invited seminar at Laboratory of Molecular Gerontology, National Institute on Aging, NIH, 2012.04.18.
59. Yusaku Nakabeppu, Quality control in the nucleotide pools is essential for cellular homeostasis, Invited seminar at National Institute of Environmental Health Science, NIH, 2012.04.16.
60. Yusaku Nakabeppu, 8-Oxoguanine, a spontaneously oxidized guanine base, promotes somatic and meiotic recombination, thus contributing to carcinogenesis and genomic diversity, Invited seminar at Laboratory of Molecular Biology, National Heart, Lung, and Blood Institute, NIH, 2012.04.10.
61. MUTYH is a potential mediator of p53 tumor suppression.
62. NUDT16 is a (deoxy)inosine diphosphatase, and its deficiency induces accumulation of single-strand breaks in nuclear DNA and growth arrest.
63. The mechanism of cell death by an oxidized nucleotide, 2-OH-ATP.
64. 8-oxoguanine increases the frequency of meiotic homologous recombination via DNA strand breaks.
65. Genome damage caused by the disruption of nucleotide pool homeostasis under environmental stress and its prevention.
66. Molecular pathologies associated with the disruption of nucleotide pool homeostasis under environmental stress.
67. The mitochondrial toxin, 3-nitropropionic acid induces MUTYH-dependent striatal neurodegeneration with accumulation of 8-oxoguanine which is effectively suppressed by OGG1 and MTH1.
68. Biological effects of 2-OH-ATP on mammalian cells.
69. Ogg1/Mth1/Mutyh triple knockout mice have a mutator phenotype exhibiting frequent hereditary congenital abnormalities.
70. Identification and functional analysis of a novel damaged nucleotide cleaning enzyme, ITPBP2.
71. Hereditary hydrocephalus occurred as a result of mutator phenotype in Ogg1, Mth1, Mutyh triple knockout mice.
72. A programmed cell death triggered by simultaneous accumulation of 8-oxoguanine in both nuclear and mitochondrial DNAs .
73. MUTYH triggers two distinct cell death pathways by monitoring 8-oxoguanine in nuclear and mitochondrial DNAs .
74. 8-Oxoguanine enhances chromosomal recombination and thus contributes genomic diversity.
75. Ogg1/Mth1/Mutyh triple knockout mice have a mutator phenotype exhibiting frequent hereditary congenital abnormalities.
Awards
  • Regulatory mechanism and biological significance of a DNA repair enzyme, MUTYH-dependent cell death
  • Research Success Award from Showa Shell Sekiyu Foundation for the Promotion of Environmental Research, 2006 「Studies on DNA damage by reactive oxygen species and its repair mechanisms」
  • General Research Award from Showa Shell Sekiyu Foundation for the Promotion of Environmental Research, 1997, 「Studies on DNA damage by reactive oxygen species and its repair mechanisms」
  • Incitement Award of the Japanese Cancer Association, 1994, 「Regulation of cell proliferation by protooncogene fos, jun」