Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Daisuke Tsuchimoto Last modified date:2021.11.02

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


Papers
1. Md Akram Hossain, Yunfeng Lin, Garrett Driscoll, Jia Li1, Anne McMahon, Joshua Matos, Haichao Zhao, Daisuke Tsuchimoto, Yusaku Nakabeppu, Jianjun Zhao and Shan Yan, APE2 Is a General Regulator of the ATR-Chk1 DNA Damage Response Pathway to Maintain Genome Integrity in Pancreatic Cancer Cells, Frontiers in cell and developmental biology, 10.3389/fcell.2021.738502, 9: 738502, 2021.11, The maintenance of genome integrity and fidelity is vital for the proper function and survival of all organisms. Recent studies have revealed that APE2 is required to activate an ATR-Chk1 DNA damage response (DDR) pathway in response to oxidative stress and a defined DNA single-strand break (SSB) in Xenopus laevis egg extracts. However, it remains unclear whether APE2 is a general regulator of the DDR pathway in mammalian cells. Here, we provide evidence using human pancreatic cancer cells that APE2 is essential for ATR DDR pathway activation in response to different stressful conditions including oxidative stress, DNA replication stress, and DNA double-strand breaks. Fluorescence microscopy analysis shows that APE2-knockdown (KD) leads to enhanced gH2AX foci and increased micronuclei formation. In addition, we identified a small molecule compound Celastrol as an APE2 inhibitor that specifically compromises the binding of APE2 but not RPA to ssDNA and 30-50 exonuclease activity of APE2 but not APE1. The impairment of ATR-Chk1 DDR pathway by Celastrol in Xenopus egg extracts and human pancreatic cancer cells highlights the physiological significance of Celastrol in the regulation of APE2 functionalities in genome integrity. Notably, cell viability assays demonstrate that APE2-KD or Celastrol sensitizes pancreatic cancer cells to chemotherapy drugs. Overall, we propose APE2 as a general regulator for the DDR pathway in genome integrity maintenance..
2. Yukino Miyachi , Takayuki Fujii, Ryo Yamasaki, Daisuke Tsuchimoto, Kyoko Iinuma, Ayako Sakoda, Shoko Fukumoto, Takuya Matsushita, Katsuhisa Masaki, Noriko Isobe, Yusaku Nakabeppu, Jun-Ichi Kira , Serum Anti-oligodendrocyte Autoantibodies in Patients With Multiple Sclerosis Detected by a Tissue-Based Immunofluorescence Assay, FRONTIERS IN NEUROLOGY, 10.3389/fneur.2021.681980, 12, 2021.08.
3. Sugako Oka, Julio Leon, Kunihiko Sakumi, Nona Abolhassani, Zijing Sheng, Daisuke Tsuchimoto, Frank M LaFerla, Yusaku Nakabeppu, MTH1 and OGG1 maintain a low level of 8-oxoguanine in Alzheimer's brain, and prevent the progression of Alzheimer's pathogenesis., Scientific reports, 10.1038/s41598-021-84640-9, 11, 1, 5819-5819, 2021.03, 8-Oxoguanine (8-oxoG), a major oxidative base lesion, is highly accumulated in Alzheimer's disease (AD) brains during the pathogenic process. MTH1 hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP, thereby avoiding 8-oxo-dG incorporation into DNA. 8-OxoG DNA glycosylase-1 (OGG1) excises 8-oxoG paired with cytosine in DNA, thereby minimizing 8-oxoG accumulation in DNA. Levels of MTH1 and OGG1 are significantly reduced in the brains of sporadic AD cases. To understand how 8-oxoG accumulation in the genome is involved in AD pathogenesis, we established an AD mouse model with knockout of Mth1 and Ogg1 genes in a 3xTg-AD background. MTH1 and OGG1 deficiency increased 8-oxoG accumulation in nuclear and, to a lesser extent, mitochondrial genomes, causing microglial activation and neuronal loss with impaired cognitive function at 4-5 months of age. Furthermore, minocycline, which inhibits microglial activation and reduces neuroinflammation, markedly decreased the nuclear accumulation of 8-oxoG in microglia, and inhibited microgliosis and neuronal loss. Gene expression profiling revealed that MTH1 and OGG1 efficiently suppress progression of AD by inducing various protective genes against AD pathogenesis initiated by Aß/Tau accumulation in 3xTg-AD brain. Our findings indicate that efficient suppression of 8-oxoG accumulation in brain genomes is a new approach for prevention and treatment of AD..
4. Yi Hu, Chun Yang, Tania Amorim, Mohsin Maqbool, Jenny Lin, Chen Li, Chuanfeng Fang, Li Xue , Ariel Kwart, Hua Fang, Mei Yin, Allison J Janocha, Daisuke Tsuchimoto, Yusaku Nakabeppu, Xiaofeng Jiang, Alex Mejia-Garcia, Faiz Anwer, Jack Khouri, Xin Qi, Qing Y Zheng, Jennifer S Yu, Shan Yan, Thomas LaFramboise, Kenneth C Anderson, Leal C Herlitz, Nikhil C Munshi, Jianhong Lin, Jianjun Zhao ,

Cisplatin-mediated upregulation of APE2 binding to MYH9 provokes mitochondrial fragmentation and acute kidney injury. , Cancer Research, 10.1158/0008-5472.CAN-20-1010, 2020.12, Cisplatin chemotherapy is standard care for many cancers but is toxic to the kidneys. How this toxicity occurs is uncertain. In this study, we identified apurinic/apyrimidinic endonuclease 2 (APE2) as a critical molecule upregulated in the proximal tubule cells (PTC) following cisplatin-induced nuclear DNA and mitochondrial DNA damage in cisplatin-treated C57B6J mice. The APE2 transgenic mouse phenotype recapitulated the pathophysiological features of C-AKI in the absence of cisplatin treatment. APE2 pulldown-MS analysis revealed that APE2 binds myosin heavy-Chain 9 (MYH9) protein in mitochondria after cisplatin treatment. Human MYH9-related disorder is caused by mutations in MYH9 that eventually lead to nephritis, macrothrombocytopenia, and deafness, a constellation of symptoms similar to the toxicity profile of cisplatin. Moreover, cisplatin-induced C-AKI was attenuated in APE2-knockout mice. Taken together, these findings suggest that cisplatin promotes AKI development by upregulating APE2, which leads to subsequent MYH9 dysfunction in PTC mitochondria due to an unrelated role of APE2 in DNA damage repair. This postulated mechanism and the availability of an engineered transgenic mouse model based on the mechanism of C-AKI provides an opportunity to identify novel targets for prophylactic treatment of this serious disease. .
5. Yuichiro Koga, Daisuke Tsuchimoto, Yoshinori Hayashi, Nona Abolhassani, Yasuto Yoneshima, Kunihiko Sakumi, Hiroshi Nakanishi, Shinya Toyokuni, Yusaku Nakabeppu, Neural stem cell-specific ITPA deficiency causes neural depolarization and epilepsy, JCI Insight, in press, 2020.11, Inosine triphosphate pyrophosphatase (ITPA) hydrolyzes inosine triphosphate (ITP) and other deaminated purine nucleotides to the corresponding nucleoside monophosphates. In humans, ITPA deficiency causes severe encephalopathy with epileptic seizure, microcephaly, and developmental retardation. In this study, we established neural stem cell-specific conditional Itpa-KO mice (Itpa-cKO mice) to clarify the effects of ITPA deficiency on the neural system. The Itpa-cKO mice showed growth retardation and died within three weeks of birth. We did not observe any microcephaly in the Itpa-cKO mice although the female Itpa-cKO mice did show adrenal hypoplasia. The Itpa-cKO mice showed limb clasping upon tail suspension and spontaneous and/or audiogenic seizure. Whole-cell patch-clamp recordings from entorhinal cortex neurons in brain slices revealed a depolarized resting membrane potential, increased firing, and frequent spontaneous miniature excitatory postsynaptic current (mEPSC) and miniature inhibitory postsynaptic current (mIPSC) in the Itpa-cKO mice compared to ITPA-proficient controls. Accumulated ITP or its metabolites, such as cyclic inosine monophosphates, or RNA containing inosines may cause membrane depolarization and hyperexcitability in neurons, and induce the phenotype of ITPA-deficient mice, including seizure..
6. Naoki Haruyama, Sakumi Kunihiko, Atsuhisa Katogi, Daisuke Tsuchimoto, Gabriele De Luca, Margherita Bignami, Yusaku Nakabeppu, 8-Oxoguanine accumulation in aged female brain impairs neurogenesis in the dentate gyrus and major island of Calleja, causing sexually dimorphic phenotypes., Progress in Neurobiology, 10.1016/j.pneurobio.2019.04.002, 2019.04.
7. Takayuki Fujii, Ryo Yamasaki, Kyoko Iinuma, Daisuke Tsuchimoto, Yoshinori Hayashi, Ban yu Saitoh, Takuya Matsushita, Mizuho A. Kido, Shinichi Aishima, Hiroshi Nakanishi, Yusaku Nakabeppu, Jun ichi Kira, A Novel Autoantibody against Plexin D1 in Patients with Neuropathic Pain, Annals of Neurology, 10.1002/ana.25279, 84, 2, 208-224, 2018.08, Objective: To identify novel autoantibodies for neuropathic pain (NeP). Methods: We screened autoantibodies that selectively bind to mouse unmyelinated C-fiber type dorsal root ganglion (DRG) neurons using tissue-based indirect immunofluorescence assays (IFA) with sera from 110 NeP patients with various inflammatory and allergic neurologic diseases or other neuropathies, and 50 controls without NeP including 20 healthy subjects and 30 patients with neurodegenerative diseases or systemic inflammatory diseases. IgG purified from IFA-positive patients' sera was subjected to Western blotting (WB) and immunoprecipitation (IP) using mouse DRG lysates. Immunoprecipitates were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) to identify target autoantigens. Results: Antiunmyelinated C-fiber type DRG neuron antibodies were more frequent in patients with NeP than non-NeP subjects (10% vs 0%; p < 0.05). These autoantibodies were all from the IgG2 subclass and colocalized mostly with isolectin B4- and P2X3-positive pain-conducting small neurons but not with S100β-positive myelinated neurons. WB revealed a common immunoreactive band (approximately 220kDa). IP and LC-MS/MS studies identified plexin D1 as a target autoantigen. Immunoadsorption tests with recombinant human plexin D1 in IFA revealed that all 11 anti–small DRG neuron antibody-positive patients had anti–plexin D1 antibodies. Application of anti–plexin D1 antibody-positive patient sera to cultured DRG neurons increased membrane permeability, leading to cellular swelling. NeP patients with anti–plexin D1 antibodies commonly developed burning pain and current perception threshold abnormalities for C-fibers. Main comorbidities were atopy and collagen-vascular disease. Immunotherapies ameliorated NeP in 7 treated cases. Interpretation: Anti–plexin D1 antibodies are a novel biomarker for immunotherapy-responsive NeP..
8. Shinji Asada, Eiko Ohta, Yoriko Akimoto, ABOLHASSANI NONA, Daisuke Tsuchimoto, Yusaku Nakabeppu, 2-Oxoadenosine induces cytotoxicity through intracellular accumulation of 2-oxo-ATP and depletion of ATP but not via the p38 MAPK pathway, SCIENTIFIC REPORTS, 10.1038/s41598-017-06636-8, 7, 2017.07.
9. M Massaad, J Zhou, Daisuke Tsuchimoto, J Chou, H Jabara, E Janssen, S Glauzy, B Olson, H Morbach, T Ohsumi, K Schmitz-Abe, M Kyriacos, J Kane, Kumiko Torisu, Yusaku Nakabeppu, LD Notarangelo, E Chouery, A Megarbane, PB Kang, Deficiency of the base excision repair enzyme NEIL3 is associated with increased lymphocyte apoptosis, autoantibodies and predisposition to autoimmunity., The Journal of Clinical Investigation, in press, 2016.10.
10. 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., Scientific Reports, 10.1038/srep32849, 6, 32849, 2016.09, Deoxyinosine (dI) occurs in DNA either by oxidative deamination of a previously incorporated deoxyadenosine residue or by misincorporation of deoxyinosine triphosphate (dITP) from the nucleotide pool during replication. To exclude dITP from the pool, mammals possess specific hydrolysing enzymes, such as inosine triphosphatase (ITPA). Previous studies have shown that deficiency in ITPA results in cell growth suppression and DNA instability. To explore the mechanisms of these phenotypes, we analysed ITPA-deficient human and mouse cells. We found that both growth suppression and accumulation of single-strand breaks in nuclear DNA of ITPA-deficient cells depended on MLH1/PMS2. The cell growth suppression of ITPA-deficient cells also depended on p53, but not on MPG, ENDOV or MSH2. ITPA deficiency significantly increased the levels of p53 protein and p21 mRNA/ protein, a well-known target of p53, in an MLH1-dependent manner. Furthermore, MLH1 may also contribute to cell growth arrest by increasing the basal level of p53 activity..
11. Kumiko Torisu, Xueli Zhang, Mari Nonaka, 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, doi: 10.1111/gtc.12402., 10:1030-1048, 2016.10, Genome-wide association studies have shown that a non-synonymous single nucleotide polymorphism in PRKCH is associated with cerebral infarction and atherosclerosis-related complications. We examined the role of PKCη in lipid metabolism and atherosclerosis using apolipoprotein E-deficient (Apoe−/−) mice. PKCη expression was augmented in the aortas of mice with atherosclerosis and exclusively detected in MOMA2-positive macrophages within atherosclerotic lesions. Prkch+/+Apoe−/− and Prkch−/−Apoe−/− mice were fed a high-fat diet (HFD), and the dyslipidemia observed in Prkch+/+Apoe−/− mice was reduced in Prkch−/−Apoe−/− mice, with a particular reduction of serum LDL cholesterol and phospholipids. Liver steatosis, which developed in Prkch+/+Apoe−/− mice, was improved in Prkch−/−Apoe−/− mice, but glucose tolerance, adipose tissue and body weight, and blood pressure were unchanged. Consistent with improvements in LDL cholesterol, atherosclerotic lesions were decreased in HFD-fed Prkch−/−Apoe−/− mice. Immunoreactivity against 3-nitrotyrosine in atherosclerotic lesions was dramatically decreased in Prkch−/−Apoe−/− mice, accompanied by decreased necrosis and apoptosis in the lesions. ARG2 mRNA and protein levels were significantly increased in Prkch−/−Apoe−/− macrophages. These data demonstrate that PKCη deficiency improves dyslipidemia and reduces susceptibility to atherosclerosis in Apoe−/− mice, revealing that PKCη plays a role in atherosclerosis development..
12. Jeroen E. J. Guikema, Erin K. Linehan, Nada Esa, Daisuke Tsuchimoto, Yusaku Nakabeppu, Robert T. Woodland, Carol E. Schrader, Apurinic/Apyrimidinic Endonuclease 2 Regulates the Expansion of Germinal Centers by Protecting against Activation-Induced Cytidine Deaminase-Independent DNA Damage in B Cells., The Journal of Immunology, 2014 Jun 16. pii: 1400002. [Epub ahead of print], 2014.06, Activation-induced cytidine deaminase (AID) initiates a process generating DNA mutations and breaks in germinal center (GC) B cells that are necessary for somatic hypermutation and class-switch recombination. GC B cells can "tolerate" DNA damage while rapidly proliferating because of partial suppression of the DNA damage response by BCL6. In this study, we develop a model to study the response of mouse GC B cells to endogenous DNA damage. We show that the base excision repair protein apurinic/apyrimidinic endonuclease (APE) 2 protects activated B cells from oxidative damage in vitro. APE2-deficient mice have smaller GCs and reduced Ab responses compared with wild-type mice. DNA double-strand breaks are increased in the rapidly dividing GC centroblasts of APE2-deficient mice, which activate a p53-independent cell cycle checkpoint and a p53-dependent apoptotic response. Proliferative and/or oxidative damage and AID-dependent damage are additive stresses that correlate inversely with GC size in wild-type, AID-, and APE2-deficient mice. Excessive double-strand breaks lead to decreased expression of BCL6, which would enable DNA repair pathways but limit GC cell numbers. These results describe a nonredundant role for APE2 in the protection of GC cells from AID-independent damage, and although GC cells uniquely tolerate DNA damage, we find that the DNA damage response can still regulate GC size through pathways that involve p53 and BCL6..
13. Janet Stavnezer, Erin K. Linehan, Mikayla R. Thompson, Ghaith Habboub, Anna J. Ucher, Tatenda Kadungure, Daisuke Tsuchimoto, Yusaku Nakabeppu, Carol E. Schrader, Differential expression of APE1 and APE2 in germinal centers promotes error-prone repair and A:T mutations during somatic hypermutation, Proceedings of the National Academy of Sciences of the United States of America , Jun 9. pii: 201405590. [Epub ahead of print], 2014.06, Somatic hypermutation (SHM) of antibody variable region genes is
initiated in germinal center B cells during an immune response by
activation-induced cytidine deaminase (AID), which converts cytosines
to uracils. During accurate repair in nonmutating cells, uracil
is excised by uracil DNA glycosylase (UNG), leaving abasic sites
that are incised by AP endonuclease (APE) to create single-strand
breaks, and the correct nucleotide is reinserted by DNA polymerase
β. During SHM, for unknown reasons, repair is error prone. There
are two APE homologs in mammals and, surprisingly, APE1, in contrast
to its high expression in both resting and in vitro-activated
splenic B cells, is expressed at very low levels in mouse germinal
center B cells where SHM occurs, and APE1 haploinsufficiency has
very little effect on SHM. In contrast, the less efficient homolog,
APE2, is highly expressed and contributes not only to the frequency
of mutations, but also to the generation of mutations at A:T base
pair (bp), insertions, and deletions. In the absence of both UNG and
APE2, mutations at A:T bp are dramatically reduced. Single-strand
breaks generated by APE2 could provide entry points for exonuclease
recruited by the mismatch repair proteins Msh2–Msh6, and the
known association of APE2 with proliferating cell nuclear antigen
could recruit translesion polymerases to create mutations at AIDinduced
lesions and also at A:T bp. Our data provide new insight
into error-prone repair of AID-induced lesions, which we propose is
facilitated by down-regulation of APE1 and up-regulation of APE2
expression in germinal center B cells..
14. Hiroko Nomaru, SAKUMI Kunihiko, 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, 10.1002/glia.22680. , 62, 8, 1284-1298, Epub 2014 Apr 25., 2014.08, The Fosb gene encodes subunits of the activator protein-1 transcription factor complex. Two mature mRNAs, Fosb and ΔFosb, encoding full-length FOSB and ΔFOSB proteins respectively, are formed by alternative splicing of Fosb mRNA. Fosb products are expressed in several brain regions. Moreover, Fosb-null mice exhibit depressive-like behaviors and adult-onset spontaneous epilepsy, demonstrating important roles in neurological and psychiatric disorders. Study of Fosb products has focused almost exclusively on neurons; their function in glial cells remains to be explored. In this study, we found that microglia express equivalent levels of Fosb and ΔFosb mRNAs to hippocampal neurons and, using microarray analysis, we identified six microglial genes whose expression is dependent on Fosb products. Of these genes, we focused on C5ar1 and C5ar2, which encode receptors for complement C5a. In isolated Fosb-null microglia, chemotactic responsiveness toward the truncated form of C5a was significantly lower than that in wild-type cells. Fosb-null mice were significantly resistant to kainate-induced seizures compared with wild-type mice. C5ar1 mRNA levels and C5aR1 immunoreactivity were increased in wild-type hippocampus 24 hours after kainate administration; however, such induction was significantly reduced in Fosb-null hippocampus. Furthermore, microglial activation after kainate administration was significantly diminished in Fosb-null hippocampus, as shown by significant reductions in CD68 immunoreactivity, morphological change and reduced levels of Il6 and Tnf mRNAs, although no change in the number of Iba-1-positive cells was observed. These findings demonstrate that, under excitotoxicity, Fosb products contribute to a neuroinflammatory response in the hippocampus through regulation of microglial C5ar1 and C5ar2 expression..
15. Zijing Sheng, Sugako Oka, Daisuke Tsuchimoto, Nona Abolhassani, Hiroko Nomaru, SAKUMI Kunihiko, Hideaki Yamada, Yusaku Nakabeppu, 8-Oxoguanine causes neurodegeneration during MUTYH-mediated DNA base excision repair, The Journal of Clinical Investigation, 10.1172/JCI65053, 122, 12, 4344-4361, 2012.12.
16. Iwama E., Tsuchimoto D., Iyama T., Sakumi K., Nakagawara A., Takayama K., Nakanishi Y., and Nakabeppu Y., Cancer-related PRUNE2 protein is associated with nucleotides and is highly expressed in mature nerve tissues., Journal of Molecular Neuroscience , Epub ahead of print, 2011.01.
17. Jeroen E.J. Guikema, Rachel M. Gerstein, Erin K. Linehan, Erin K. Clohert, Eric Evan-Browning, Daisuke Tsuchimoto, Yusaku Nakabeppu, and Carol E. Schrader, AP-Endonuclease 2 is necessary for normal B cell development and recovery of lymphoid progenitors after chemotherapeutic challenge., Journal of Immunology, 186(4), 1943-50, 2011.02.
18. 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, doi:10.1093/nar/gkq249 , 38(14), 4834-43, 2010.08.
19. 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 Res., 2010 May;38(9):2891-903., 2010.05.
20. Behmanesh M, Sakumi K, Abolhassani N, Toyokuni S, Oka S, Ohnishi YN, Tsuchimoto D, Nakabeppu Y, ITPase-deficient mice show growth retardation and die before weaning, Cell Death and Differentiation , 2009 Jun 5. [Epub ahead of print], 2009.06.
21. Nonaka M, Tsuchimoto D, Sakumi K, Nakabeppu Y. , Mouse RS21-C6 is a mammalian 2'-deoxycytidine 5'-triphosphate pyrophosphohydrolase that prefers 5-iodocytosine. , FEBS J. , 276(6):1654-1666, 2009.03.
22. Kajitani K, Nomaru H, Ifuku M, Yutsudo N, Dan Y, Miura T, Tsuchimoto D, Sakumi K, Kadoya T, Horie H, Poirier F, Noda M, 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.
23. 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 (Amst), 7(9):1437-1454., 2008.09.
24. 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., The EMBO Journal, 27(2):421-432, 2008.01.
25. Guikema JEJ, Kinehan EK, Tsuchimoto D, Nakabeppu Y, Strauss PR, Stavnezer J, and Schrader CE, APE1- and APE2-dependent DNA breaks in immunoglobulin class switch recombination, The Journal of Experimental Medicine, 204(12):3017-3026, 2007.11.
26. Ohno M., Miura T., Furuichi M., Tominaga Y., Tsuchimoto D., Sakumi K. and 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 Research, 16:567-575, 2006.05.
27. Torisu K., Tsuchimoto D., Ohnishi Y. and Nakabeppu Y., Hematopoietic tissue-specific expression of mouse Neil3 for Endonuclease VIII-like protein., The Journal of Biochemistry, 10.1093/jb/mvi168, 138, 6, 763-772, 138(6):763-772, 2005.12.
28. Ushijima Y., Tominaga Y, Miura T, Tsuchimoto D, Sakumi K and Nakabeppu Y., A functional analysis of the DNA glycosylase activity of mouse MUTYH protein excising 2-hydroxyadenine opposite guanine in DNA., Nucleic Acids Research, 10.1093/nar/gki214, 33, 2, 672-682, 33(2):672-682, 2005.01.
29. Behmanesh B., Sakumi K., Tsuchimoto D., Torisu K., Ohnishi-Honda Y., Rancourt D.E. and Nakabeppu Y., Characterization of the structure and expression of mouse Itpa gene and its related sequences in the mouse genome., DNA Research, 10.1093/dnares/12.1.39, 12, 1, 39-51, 12:29-41, 2005.02.
30. Ide Y, Tsuchimoto D, Tominaga Y, Nakashima M, Watanabe T, Sakumi K, Ohno M, Nakabeppu Y., Growth retardation and dyslymphopoiesis accompanied by G2/M arrest in APEX2-null mice., Blood, 10.1182/blood-2004-04-1476, 104, 13, 4097-4103, 104(13):4097-4103, 2004.12.
31. Tsuchimoto D, Tojo A, Asano S, A Mechanism of Transcriptional Regulation of the CSF-1 Gene by Interferon-gamma., Immunological Investigations, 10.1081/IMM-200038662, 33, 4, 397-405, 33(4):397-405, 2004.12.
32. Tominaga Y, Ushijima Y, Tsuchimoto D, Mishima M, Shirakawa M, Hirano S, Sakumi K, Nakabeppu Y., MUTYH prevents OGG1 or APEX1 from inappropriately processing its substrate or reaction product with its C-terminal domain, Nucleic Acids Research, 10.1093/nar/gkh642, 32, 10, 3198-3211, 32(10):3198-3211, 2004.06.
33. Miura T, Takahashi M, Horie H, Kurushima H, Tsuchimoto D, Sakumi K, Nakabeppu Y., 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, 10.1038/sj.cdd.4401462, 11, 10, 1076-1083, 11(10):1076-1083, 2004.10.
34. Nakabeppu Y, Tsuchimoto D, Ichinoe A, Ohno M, Ide Y, Hirano S, Yoshimura D, Tominaga Y, Furuichi M, Sakumi K., Biological significance of the defense mechanisms against oxidative damage in nucleic acids caused by reactive oxygen species: from mitochondria to nuclei, Ann N Y Acad Sci., 10.1196/annals.1293.011, 1011, 101-111, 1011:101-111, 2004.04.
35. Ichinoe A, Behmanesh M, Tominaga Y, Ushijima Y, Hirano S, Sakai Y, Tsuchimoto D, Sakumi K, Wake N, Nakabeppu Y., Identification and characterization of two forms of mouse MUTYH proteins encoded by alternatively spliced transcripts, Nucleic Acids Research, 10.1093/nar/gkh214, 32, 2, 477-487, 32(2):477-487, 2004.01.
36. Hirano S, Tominaga Y, Ichinoe A, Ushijima Y, Tsuchimoto D, Honda-Ohnishi Y,, Mutator phenotype of MUTYH-null mouse embryonic stem cells., J Biol Chem., 10.1074/jbc.C300316200, 278, 40, 38121-38124, 278(40):38121-38124, 2003.10.
37. Tahara K, Tsuchimoto D, Tominaga Y, Asoh S, Ohta S, Kitagawa M, Horie H, Nakabeppu Y, DeltaFosB, but not FosB, induces delayed apoptosis independent of cell
proliferation in the Rat1a embryo cell line., Cell Death Differ., 10.1038/sj.cdd.4401173, 10, 5, 496-507, 10(5):496-507., 2003.05.
38. Ide Y, Tsuchimoto D, Tominaga Y, Iwamoto Y, Nakabeppu Y., Characterization of the genomic structure and expression of the mouse Apex2
gene., Genomics, 10.1016/S0888-7543(02)00009-5, 81, 1, 47-57, 81(1):47-57., 2003.01.
39. Tsuchimoto D, Sakai Y, Sakumi K, Nishioka K, Sasaki M, Fujiwara T, Nakabeppu Y, 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., 10.1093/nar/29.11.2349, 29, 11, 2349-2360, 29(11):2349-2360, 2001.06.