Yusaku Nakabeppu

Apex2 is required for efficient somatic hypermutation but not for class switch recombination of immunoglobulin genes (2009)

Sabouri, Zahra, Okazaki, Il-mi, Shinkura, Reiko, Begum, Nasim, Nagaoka, Hitoshi, Tsuchimoto, Daisuke, ...

The DNA cleavage step in both the class switch recombination (CSR) and somatic hypermutation (SHM) of Ig genes is initiated by activation-induced cytidine deaminase (AID). However, the detailed...

APE1- and APE2-dependent DNA breaks in immunoglobulin class switch recombination (2007)

Guikema, Jeroen E. J., Linehan, Erin K., Tsuchimoto, Daisuke, Nakabeppu, Yusaku, Strauss, Phyllis R., Stavnezer, Janet, ...

Antibody class switch recombination (CSR) occurs by an intrachromosomal deletion requiring generation of double-stranded breaks (DSBs) in switch-region DNA. The initial steps in DSB formation have...

Prevention of the Mutagenecity and Cytotoxicity of Oxidized Purine Nucleotides (2007)

Nakabeppu, Yusaku, Behmanesh, Mehrdad, Yamaguchi, Hiroo, Yoshimura, Daisuke, Sakumi, Kunihiko, 中別府, 雄作, ...

Damage to nucleic acids is particularly hazardous because the genetic information in genomic DNA, such as nuclear and mitochondrial DNA, can be altered. Damage accumulated in cellular DNAs often...

Oxidative damage in nucleic acids and Parkinson's disease. (2007)

Nakabeppu, Yusaku, Tsuchimoto, Daisuke, Yamaguchi, Hiroo, Sakumi, Kunihiko, 中別府, 雄作, 土本, 大介, ...

Oxidative DNA lesions, such as 8-oxoguanine (8-oxoG), accumulate in nuclear and mitochondrial genomes during aging, and such accumulation can increase dramatically in patients with Parkinson's...

Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy. (2006)

Thijssen, Victor, Postel, Ruben, Brandwijk, Ricardo, Dings, Ruud, Nesmelova, Irina, Satijn, Sietske, ...

We describe that galectin-1 (gal-1) is a receptor for the angiogenesis inhibitor anginex, and that the protein is crucial for tumor angiogenesis. gal-1 is overexpressed in endothelial cells of...

Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy. (2006)

Thijssen, Victor, Postel, Ruben, Brandwijk, Ricardo, Dings, Ruud, Nesmelova, Irina, Satijn, Sietske, ...

We describe that galectin-1 (gal-1) is a receptor for the angiogenesis inhibitor anginex, and that the protein is crucial for tumor angiogenesis. gal-1 is overexpressed in endothelial cells of...

A genome-wide distribution of 8-oxoguanine correlates with the preferred regions for recombination and single nucleotide polymorphism in the human genome (2006)

Ohno, Mizuki, Miura, Tomofumi, Furuichi, Masato, Tominaga, Yohei, Tsuchimoto, Daisuke, Sakumi, Kunihiko, ...

8-Oxoguanine (8-oxoG), a major spontaneous form of oxidative DNA damage, is considered to be a natural cause of genomic diversity in organisms because of its mutagenic potential. The steady-state...

Recognition of Nucleotide Analogs Containing the 7,8-Dihydro-8-oxo Structure by the Human MTH1 Protein (2006)

Kamiya, Hiroyuki, Cadena-Amaro, Claudio, Dugué, Laurence, Yakushiji, Hiroyuki, Minakawa, Noriaki, Matsuda, Akira, ...

The MTH1 protein catalyzes hydrolysis of oxidatively damaged purine nucleotides including 8-hydroxy-dGTP to the monophosphates. The MTH1 protein seems to act as an important defense system against...

Recognition of Nucleotide Analogs Containing the 7,8-Dihydro-8-oxo Structure by the Human MTH1 Protein (2006)

Kamiya, Hiroyuki, Cadena-Amaro, Claudio, Dugué, Laurence, Yakushiji, Hiroyuki, Minakawa, Noriaki, Matsuda, Akira, ...

The MTH1 protein catalyzes hydrolysis of oxidatively damaged purine nucleotides including 8-hydroxy-dGTP to the monophosphates. The MTH1 protein seems to act as an important defense system against...

Characterization of the Structure and Expression of Mouse Itpa Gene and its Related Sequences in the Mouse Genome (2005)

Behmanesh, Mehrdad, Sakumi, Kunihiko, Tsuchimoto, Daisuke, Torisu, Kumiko, Ohnishi-Honda, Yoko, Rancourt, Derrick E., ...

In the mouse genome, we found one processed Itpa gene-like sequence and two processed Itpa pseudogenes as well as the Itpa gene itself with introns, located on chromosome 2F3, which was isolated by a...

Hematopoietic Tissue-Specific Expression of Mouse Neil3 for Endonuclease VIII-Like Protein (2005)

Torisu, Kumiko, Tsuchimoto, Daisuke, Ohnishi, Yoshinori, Nakabeppu, Yusaku

We cloned cDNA and genomic DNA containing exon 1 of mouse Neil3. Neil3 spans 52.4 kb and consists of 10 exons. Northern blot analysis revealed that Neil3 mRNA was selectively expressed in thymus,...

A functional analysis of the DNA glycosylase activity of mouse MUTYH protein excising 2-hydroxyadenine opposite guanine in DNA (2005)

Ushijima, Yasuhiro, Tominaga, Yohei, Miura, Tomofumi, Tsuchimoto, Daisuke, Sakumi, Kunihiko, Nakabeppu, Yusaku

2-Hydroxy-2-deoxyadenosine triphosphate (2-OH-dATP), generated by the oxidation of dATP, can be misincorporated by DNA polymerases opposite guanine in template DNA during DNA replication, thus...

Identification and characterization of two forms of mouse MUTYH proteins encoded by alternatively spliced transcripts (2004)

Ichinoe, Akimasa, Behmanesh, Mehrdad, Tominaga, Yohei, Ushijima, Yasuhiro, Hirano, Seiki, Sakai, Yasunari, ...

There are three types of mouse Mutyh mRNAs (type a, b and c) generated by alternative splicing, and type b mRNA is a major form among the three in most of the tissues examined. The level of type c...

MUTYH prevents OGG1 or APEX1 from inappropriately processing its substrate or reaction product with its C-terminal domain (2004)

Tominaga, Yohei, Ushijima, Yasuhiro, Tsuchimoto, Daisuke, Mishima, Masaki, Shirakawa, Masahiro, Hirano, Seiki, ...

MutY homolog (MUTYH) excises adenine opposite 8-oxoguanine (8-oxoG) in DNA, thus preventing occurrence of G:C to T:A transversion. In cell-free extract prepared from the thymocytes of wild type but...

A novel Nudix hydrolase for oxidized purine nucleoside triphosphates encoded by ORFYLR151c (PCD1 gene) in Saccharomyces cerevisiae (2004)

Nunoshiba, Tatsuo, Ishida, Rikiya, Sasaki, Michi, Iwai, Shigenori, Nakabeppu, Yusaku, Yamamoto, Kazuo

A search for candidates for a functional homologue of Escherichia coli MutT in yeast Saccharomyces cerevisiae was made in the NCBI-BLAST database using the Nudix box, a short amino acid sequence...

Futile short-patch DNA base excision repair of adenine:8-oxoguanine mispair (2004)

Hashimoto, Keiji, Tominaga, Yohei, Nakabeppu, Yusaku, Moriya, Masaaki

8-Oxo-7, 8-dihydrodeoxyguanosine (8-oxo-dG), one of the representative oxidative DNA lesions, frequently mispairs with the incoming dAMP during mammalian DNA replication. Mispaired dA is removed by...

fosB Gene Products Trigger Cell Proliferation and Morphological Alteration with an Increased Expression of a Novel Processed From of Galectin-1 in the Rat 3Y1 Embroyo Cell Line (2002)

Nishioka, Tomoko, Sakumi, Kunihiko, Miura, Tomofumi, Tahara, Kazuki, Horie, Hidenori, Kadoya, Toshihiko, ...

In this study, we established rat 3Y1 embryo cell lines expressing FosB and AFosB as fusion proteins (ER-FosB, ER-AFosB) with the ligand-binding domain of human estrogen receptor (ER). The binding of...

Substrate recognition by the human MTH1 protein (2002)

Kamiya, Hiroyuki, Dugué, Laurence, Yakushiji, Hiroyuki, Pochet, Sylvie, Nakabeppu, Yusaku, Harashima, Hideyoshi

Substrate recognition by the human MTH1 protein (2002)

Kamiya, Hiroyuki, Dugué, Laurence, Yakushiji, Hiroyuki, Pochet, Sylvie, Nakabeppu, Yusaku, Harashima, Hideyoshi

A nucleotide pool sanitizing enzyme, the human MIH1 protein, hydrolyses 2-hydroxy-dATP, 8-hydroxy-dATP, and 8-hydroxy-dGTP. To examine the substrate recognition mechanism of the MTH1 protein, ten...

Accumulation of 8-oxo-2'-deoxyguanosine and increased expression of hMTH1 protein in brain tumors (2001)

Iida, Takashi, Furuta, Akiko, Kawashima, Masatou, Nishida, Jun-ichi, Nakabeppu, Yusaku, Iwaki, Toru, ...

Oxidative DNA damage generated by an attack of reactive oxygen species causes mutation or cell death that may lead to various diseases and may be related to initiation or progression of...

Accumulation of 8-oxo-2'-deoxyguanosine and increased expression of hMTH1 protein in brain tumors (2001)

Iida, Takashi, Furuta, Akiko, Kawashima, Masatou, Nishida, Jun-ichi, Nakabeppu, Yusaku, Iwaki, Toru

Oxidative DNA damage generated by an attack of reactive oxygen species causes mutation or cell death that may lead to various diseases and may be related to initiation or progression of...

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 (2001)

Tsuchimoto, Daisuke, Sakai, Yasunari, Sakumi, Kunihiko, Nishioka, Kenichi, Sasaki, Masafumi, Fujiwara, Toshiyuki, ...

In human cells APE1 is the major AP endonuclease and it has been reported to have no functional mitochondrial targeting sequence (MTS). We found that APE2 protein possesses a putative MTS. When its...

Human MTH1 protein hydrolyzes the oxidized ribonucleotide, 2-hydroxy-ATP (2001)

Fujikawa, Katsuyoshi, Kamiya, Hiroyuki, Yakushiji, Hiroyuki, Nakabeppu, Yusaku, Kasai, Hiroshi

The human nucleotide pool sanitization enzyme, MTH1, hydrolyzes 2-hydroxy-dATP and 8-hydroxy-dATP in addition to 8-hydroxy-dGTP. We report here that human MTH1 is highly specific for 2-hydroxy-ATP,...

Identification of human MutY homolog (hMYH) as a repair enzyme for 2-hydroxyadenine in DNA and detection of multiple forms of hMYH located in nuclei and mitochondria (2000)

Ohtsubo, Toshio, Nishioka, Kenichi, Imaiso, Yasuyuki, Iwai, Shigenori, Shimokawa, Hidetoshi, Oda, Hisanobu, ...

An enzyme activity introducing an alkali-labile site at 2-hydroxyadenine (2-OH-A) in double-stranded oligonucleotides was detected in nuclear extracts of Jurkat cells. This activity co-eluted with...

Functional significance of conserved residues in the phosphohydrolase module of Escherichia coli MutT protein (2000)

Shimokawa, Hidetoshi, Fujii, Yoshimitsu, Furuichi, Masato, Sekiguchi, Mutsuo, Nakabeppu, Yusaku

Escherichia coli MutT protein hydrolyzes 8-oxo-7,8-dihydro-2′-dGTP (8-oxo-dGTP) to the monophosphate, thus avoiding the incorporation of 8-oxo-7,8-dihydroguanine (8-oxo-G) into nascent DNA....

A defect in a single allele of the Mlh1 gene causes dissociation of the killing and tumorigenic actions of an alkylating carcinogen in methyltransferase-deficient mice (2000)

Kawate, Hisaya, Itoh, Riyoko, Sakumi, Kunihiko, Nakabeppu, Yusaku, Tsuzuki, Teruhisa, Ide, Fumio, ...

Mice with mutations in both alleles of the Mgmt and the Mlh1 gene, the former encoding a DNA repair methyltransferase and the latter a protein functioning at an early step of mismatch repair, are as...

A unique structural feature of rabbit DNA repair methyltransferase as revealed by cDNA cloning (1994)

Iyama, Akihiro, Sakumi, Kunihiko, Nakabeppu, Yusaku, Sekiguchi, Mutsuo

cDNA encoding rabbit O6-methylguanine-DNA methyl transferase that repairs DNA damaged by alkylating agents was isolated, using as a probe a fragment of mouse cDNA coding for a region containing the...

Action of T4 Endonuclease V on Polydeoxyribonucleotides with Apyrimidinic or Apurinic Sites (1982)

NAKATSU, Yoshimichi, NAKABEPPU, Yusaku, SEKIGUCHI, Mutsuo

[3H]Thymine-labeled poly(dT) carrying many apyrimidinic (AP) sites has been prepared by treating an enzymatically synthesized poly(dA) poly(dT, dU) with uracil-DNA glycosylase. Incubation of the...

Human MTH1 protein hydrolyzes the oxidized ribonucleotide, 2-hydroxy-ATP

Fujikawa, Katsuyoshi, Kamiya, Hiroyuki, Yakushiji, Hiroyuki, Nakabeppu, Yusaku, Kasai, Hiroshi

The human nucleotide pool sanitization enzyme, MTH1, hydrolyzes 2-hydroxy-dATP and 8-hydroxy-dATP in addition to 8-hydroxy-dGTP. We report here that human MTH1 is highly specific for 2-hydroxy-ATP,...

Expression and Differential Intracellular Localization of Two Major Forms of Human 8-Oxoguanine DNA Glycosylase Encoded by Alternatively Spliced OGG1 mRNAs

Nishioka, Kenichi, Ohtsubo, Toshio, Oda, Hisanobu, Fujiwara, Toshiyuki, Kang, Dongchon, Sugimachi, Keizo, ...

We identified seven alternatively spliced forms of human 8-oxoguanine DNA glycosylase (OGG1) mRNAs, classified into two types based on their last exons (type 1 with exon 7: 1a and 1b; type 2 with...

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

Tsuchimoto, Daisuke, Sakai, Yasunari, Sakumi, Kunihiko, Nishioka, Kenichi, Sasaki, Masafumi, Fujiwara, Toshiyuki, ...

In human cells APE1 is the major AP endonuclease and it has been reported to have no functional mitochondrial targeting sequence (MTS). We found that APE2 protein possesses a putative MTS. When its...

Spontaneous tumorigenesis in mice defective in the MTH1 gene encoding 8-oxo-dGTPase

Tsuzuki, Teruhisa, Egashira, Akinori, Igarashi, Hisato, Iwakuma, Tomoo, Nakatsuru, Yoko, Tominaga, Yohei, ...

Oxygen radicals, which can be produced through normal cellular metabolism, are thought to play an important role in mutagenesis and tumorigenesis. Among various classes of oxidative DNA damage,...

JSAP1, a Novel Jun N-Terminal Protein Kinase (JNK)-Binding Protein That Functions as a Scaffold Factor in the JNK Signaling Pathway

Ito, Michihiko, Yoshioka, Katsuji, Akechi, Mizuho, Yamashita, Shinya, Takamatsu, Nobuhiko, Sugiyama, Kenji, ...

The major components of the mitogen-activated protein kinase (MAPK) cascades are MAPK, MAPK kinase (MAPKK), and MAPKK kinase (MAPKKK). Recent rapid progress in identifying members of MAPK cascades...

Functional significance of conserved residues in the phosphohydrolase module of Escherichia coli MutT protein

Shimokawa, Hidetoshi, Fujii, Yoshimitsu, Furuichi, Masato, Sekiguchi, Mutsuo, Nakabeppu, Yusaku

Escherichia coli MutT protein hydrolyzes 8-oxo-7,8-dihydro-2′-dGTP (8-oxo-dGTP) to the monophosphate, thus avoiding the incorporation of 8-oxo-7,8-dihydroguanine (8-oxo-G) into nascent DNA....

Identification of human MutY homolog (hMYH) as a repair enzyme for 2-hydroxyadenine in DNA and detection of multiple forms of hMYH located in nuclei and mitochondria

Ohtsubo, Toshio, Nishioka, Kenichi, Imaiso, Yasuyuki, Iwai, Shigenori, Shimokawa, Hidetoshi, Oda, Hisanobu, ...

An enzyme activity introducing an alkali-labile site at 2-hydroxyadenine (2-OH-A) in double-stranded oligonucleotides was detected in nuclear extracts of Jurkat cells. This activity co-eluted with...

The Oxidized Deoxynucleoside Triphosphate Pool Is a Significant Contributor to Genetic Instability in Mismatch Repair-Deficient Cells

Russo, Maria Teresa, Blasi, Monica Francesca, Chiera, Federica, Fortini, Paola, Degan, Paolo, Macpherson, Peter, ...

Oxidation is a common form of DNA damage to which purines are particularly susceptible. We previously reported that oxidized dGTP is potentially an important source of DNA 8-oxodGMP in mammalian...

Identification and characterization of two forms of mouse MUTYH proteins encoded by alternatively spliced transcripts

Ichinoe, Akimasa, Behmanesh, Mehrdad, Tominaga, Yohei, Ushijima, Yasuhiro, Hirano, Seiki, Sakai, Yasunari, ...

There are three types of mouse Mutyh mRNAs (type a, b and c) generated by alternative splicing, and type b mRNA is a major form among the three in most of the tissues examined. The level of type c...

MUTYH prevents OGG1 or APEX1 from inappropriately processing its substrate or reaction product with its C-terminal domain

Tominaga, Yohei, Ushijima, Yasuhiro, Tsuchimoto, Daisuke, Mishima, Masaki, Shirakawa, Masahiro, Hirano, Seiki, ...

MutY homolog (MUTYH) excises adenine opposite 8-oxoguanine (8-oxoG) in DNA, thus preventing occurrence of G:C to T:A transversion. In cell-free extract prepared from the thymocytes of wild type but...

A novel Nudix hydrolase for oxidized purine nucleoside triphosphates encoded by ORFYLR151c (PCD1 gene) in Saccharomyces cerevisiae

Nunoshiba, Tatsuo, Ishida, Rikiya, Sasaki, Michi, Iwai, Shigenori, Nakabeppu, Yusaku, Yamamoto, Kazuo

A search for candidates for a functional homologue of Escherichia coli MutT in yeast Saccharomyces cerevisiae was made in the NCBI-BLAST database using the Nudix box, a short amino acid sequence...

Futile short-patch DNA base excision repair of adenine:8-oxoguanine mispair

Hashimoto, Keiji, Tominaga, Yohei, Nakabeppu, Yusaku, Moriya, Masaaki

8-Oxo-7, 8-dihydrodeoxyguanosine (8-oxo-dG), one of the representative oxidative DNA lesions, frequently mispairs with the incoming dAMP during mammalian DNA replication. Mispaired dA is removed by...

A functional analysis of the DNA glycosylase activity of mouse MUTYH protein excising 2-hydroxyadenine opposite guanine in DNA

Ushijima, Yasuhiro, Tominaga, Yohei, Miura, Tomofumi, Tsuchimoto, Daisuke, Sakumi, Kunihiko, Nakabeppu, Yusaku

2-Hydroxy-2-deoxyadenosine triphosphate (2-OH-dATP), generated by the oxidation of dATP, can be misincorporated by DNA polymerases opposite guanine in template DNA during DNA replication, thus...

Stress response gene ATF3 is a target of c-myc in serum-induced cell proliferation

Tamura, Kiyoshi, Hua, Bayin, Adachi, Susumu, Guney, Isil, Kawauchi, Junya, Morioka, Masaki, ...

The c-myc proto-oncogene encodes a transcription factor that promotes cell cycle progression and cell proliferation, and its deficiency results in severely retarded proliferation rates. The ATF3...

A genome-wide distribution of 8-oxoguanine correlates with the preferred regions for recombination and single nucleotide polymorphism in the human genome

Ohno, Mizuki, Miura, Tomofumi, Furuichi, Masato, Tominaga, Yohei, Tsuchimoto, Daisuke, Sakumi, Kunihiko, ...

8-Oxoguanine (8-oxoG), a major spontaneous form of oxidative DNA damage, is considered to be a natural cause of genomic diversity in organisms because of its mutagenic potential. The steady-state...

Human MTH1 protein hydrolyzes the oxidized ribonucleotide, 2-hydroxy-ATP

Fujikawa, Katsuyoshi, Kamiya, Hiroyuki, Yakushiji, Hiroyuki, Nakabeppu, Yusaku, Kasai, Hiroshi

The human nucleotide pool sanitization enzyme, MTH1, hydrolyzes 2-hydroxy-dATP and 8-hydroxy-dATP in addition to 8-hydroxy-dGTP. We report here that human MTH1 is highly specific for 2-hydroxy-ATP,...

Expression and Differential Intracellular Localization of Two Major Forms of Human 8-Oxoguanine DNA Glycosylase Encoded by Alternatively Spliced OGG1 mRNAs

Nishioka, Kenichi, Ohtsubo, Toshio, Oda, Hisanobu, Fujiwara, Toshiyuki, Kang, Dongchon, Sugimachi, Keizo, ...

We identified seven alternatively spliced forms of human 8-oxoguanine DNA glycosylase (OGG1) mRNAs, classified into two types based on their last exons (type 1 with exon 7: 1a and 1b; type 2 with...

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

Tsuchimoto, Daisuke, Sakai, Yasunari, Sakumi, Kunihiko, Nishioka, Kenichi, Sasaki, Masafumi, Fujiwara, Toshiyuki, ...

In human cells APE1 is the major AP endonuclease and it has been reported to have no functional mitochondrial targeting sequence (MTS). We found that APE2 protein possesses a putative MTS. When its...

Spontaneous tumorigenesis in mice defective in the MTH1 gene encoding 8-oxo-dGTPase

Tsuzuki, Teruhisa, Egashira, Akinori, Igarashi, Hisato, Iwakuma, Tomoo, Nakatsuru, Yoko, Tominaga, Yohei, ...

Oxygen radicals, which can be produced through normal cellular metabolism, are thought to play an important role in mutagenesis and tumorigenesis. Among various classes of oxidative DNA damage,...

JSAP1, a Novel Jun N-Terminal Protein Kinase (JNK)-Binding Protein That Functions as a Scaffold Factor in the JNK Signaling Pathway

Ito, Michihiko, Yoshioka, Katsuji, Akechi, Mizuho, Yamashita, Shinya, Takamatsu, Nobuhiko, Sugiyama, Kenji, ...

The major components of the mitogen-activated protein kinase (MAPK) cascades are MAPK, MAPK kinase (MAPKK), and MAPKK kinase (MAPKKK). Recent rapid progress in identifying members of MAPK cascades...

Functional significance of conserved residues in the phosphohydrolase module of Escherichia coli MutT protein

Shimokawa, Hidetoshi, Fujii, Yoshimitsu, Furuichi, Masato, Sekiguchi, Mutsuo, Nakabeppu, Yusaku

Escherichia coli MutT protein hydrolyzes 8-oxo-7,8-dihydro-2′-dGTP (8-oxo-dGTP) to the monophosphate, thus avoiding the incorporation of 8-oxo-7,8-dihydroguanine (8-oxo-G) into nascent DNA....

Identification of human MutY homolog (hMYH) as a repair enzyme for 2-hydroxyadenine in DNA and detection of multiple forms of hMYH located in nuclei and mitochondria

Ohtsubo, Toshio, Nishioka, Kenichi, Imaiso, Yasuyuki, Iwai, Shigenori, Shimokawa, Hidetoshi, Oda, Hisanobu, ...

An enzyme activity introducing an alkali-labile site at 2-hydroxyadenine (2-OH-A) in double-stranded oligonucleotides was detected in nuclear extracts of Jurkat cells. This activity co-eluted with...

The Oxidized Deoxynucleoside Triphosphate Pool Is a Significant Contributor to Genetic Instability in Mismatch Repair-Deficient Cells

Russo, Maria Teresa, Blasi, Monica Francesca, Chiera, Federica, Fortini, Paola, Degan, Paolo, Macpherson, Peter, ...

Oxidation is a common form of DNA damage to which purines are particularly susceptible. We previously reported that oxidized dGTP is potentially an important source of DNA 8-oxodGMP in mammalian...

Identification and characterization of two forms of mouse MUTYH proteins encoded by alternatively spliced transcripts

Ichinoe, Akimasa, Behmanesh, Mehrdad, Tominaga, Yohei, Ushijima, Yasuhiro, Hirano, Seiki, Sakai, Yasunari, ...

There are three types of mouse Mutyh mRNAs (type a, b and c) generated by alternative splicing, and type b mRNA is a major form among the three in most of the tissues examined. The level of type c...

MUTYH prevents OGG1 or APEX1 from inappropriately processing its substrate or reaction product with its C-terminal domain

Tominaga, Yohei, Ushijima, Yasuhiro, Tsuchimoto, Daisuke, Mishima, Masaki, Shirakawa, Masahiro, Hirano, Seiki, ...

MutY homolog (MUTYH) excises adenine opposite 8-oxoguanine (8-oxoG) in DNA, thus preventing occurrence of G:C to T:A transversion. In cell-free extract prepared from the thymocytes of wild type but...

A novel Nudix hydrolase for oxidized purine nucleoside triphosphates encoded by ORFYLR151c (PCD1 gene) in Saccharomyces cerevisiae

Nunoshiba, Tatsuo, Ishida, Rikiya, Sasaki, Michi, Iwai, Shigenori, Nakabeppu, Yusaku, Yamamoto, Kazuo

A search for candidates for a functional homologue of Escherichia coli MutT in yeast Saccharomyces cerevisiae was made in the NCBI-BLAST database using the Nudix box, a short amino acid sequence...

Futile short-patch DNA base excision repair of adenine:8-oxoguanine mispair

Hashimoto, Keiji, Tominaga, Yohei, Nakabeppu, Yusaku, Moriya, Masaaki

8-Oxo-7, 8-dihydrodeoxyguanosine (8-oxo-dG), one of the representative oxidative DNA lesions, frequently mispairs with the incoming dAMP during mammalian DNA replication. Mispaired dA is removed by...

A functional analysis of the DNA glycosylase activity of mouse MUTYH protein excising 2-hydroxyadenine opposite guanine in DNA

Ushijima, Yasuhiro, Tominaga, Yohei, Miura, Tomofumi, Tsuchimoto, Daisuke, Sakumi, Kunihiko, Nakabeppu, Yusaku

2-Hydroxy-2-deoxyadenosine triphosphate (2-OH-dATP), generated by the oxidation of dATP, can be misincorporated by DNA polymerases opposite guanine in template DNA during DNA replication, thus...

Stress response gene ATF3 is a target of c-myc in serum-induced cell proliferation

Tamura, Kiyoshi, Hua, Bayin, Adachi, Susumu, Guney, Isil, Kawauchi, Junya, Morioka, Masaki, ...

The c-myc proto-oncogene encodes a transcription factor that promotes cell cycle progression and cell proliferation, and its deficiency results in severely retarded proliferation rates. The ATF3...

A genome-wide distribution of 8-oxoguanine correlates with the preferred regions for recombination and single nucleotide polymorphism in the human genome

Ohno, Mizuki, Miura, Tomofumi, Furuichi, Masato, Tominaga, Yohei, Tsuchimoto, Daisuke, Sakumi, Kunihiko, ...

8-Oxoguanine (8-oxoG), a major spontaneous form of oxidative DNA damage, is considered to be a natural cause of genomic diversity in organisms because of its mutagenic potential. The steady-state...

Contrasting Genome-Wide Distribution of 8-Hydroxyguanine and Acrolein-Modified Adenine during Oxidative Stress-Induced Renal Carcinogenesis

Akatsuka, Shinya, Aung, Than Tin, Dutta, Khokon Kumar, Jiang, Li, Lee, Wen-Hua, Liu, Yu-Ting, ...

Oxidative stress is a persistent threat to the genome and is associated with major causes of human mortality, including cancer, atherosclerosis, and aging. Here we established a method to generate...

Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy

Postel, Ruben, Dings, Ruud P. M., Nesmelova, Irina, Satijn, Sietske, ...

We describe that galectin-1 (gal-1) is a receptor for the angiogenesis inhibitor anginex, and that the protein is crucial for tumor angiogenesis. gal-1 is overexpressed in endothelial cells of...

Differential Expression of Cytokeratin after Orthotopic Implantation of Newly Established Human Tongue Cancer Cell Lines of Defined Metastatic Ability

Morifuji, Masayo, Taniguchi, Shun’ichiro, Sakai, Hidetaka, Nakabeppu, Yusaku, Ohishi, Masamichi

Two human tongue squamous cell carcinoma cell lines, SQUU-A and SQUU-B, were established from the same patient. Cervical lymph node metastasis was detected in the mice orthotopically implanted with...

Novel role of neuronal Ca2+ sensor-1 as a survival factor up-regulated in injured neurons

Nakamura, Tomoe Y., Jeromin, Andreas, Smith, George, Kurushima, Hideaki, Koga, Hitoshi, Nakabeppu, Yusaku, ...

A molecular basis of survival from neuronal injury is essential for the development of therapeutic strategy to remedy neurodegenerative disorders. In this study, we demonstrate that an EF-hand...

APE1- and APE2-dependent DNA breaks in immunoglobulin class switch recombination

Guikema, Jeroen E.J., Linehan, Erin K., Tsuchimoto, Daisuke, Nakabeppu, Yusaku, Strauss, Phyllis R., Stavnezer, Janet, ...

Antibody class switch recombination (CSR) occurs by an intrachromosomal deletion requiring generation of double-stranded breaks (DSBs) in switch-region DNA. The initial steps in DSB formation have...

APE1- and APE2-dependent DNA breaks in immunoglobulin class switch recombination

Guikema, Jeroen E.J., Linehan, Erin K., Tsuchimoto, Daisuke, Nakabeppu, Yusaku, Strauss, Phyllis R., Stavnezer, Janet, ...

A Role for Oxidized DNA Precursors in Huntington's Disease–Like Striatal Neurodegeneration

De Luca, Gabriele, Russo, Maria Teresa, Degan, Paolo, Tiveron, Cecilia, Zijno, Andrea, Meccia, Ettore, ...

Several human neurodegenerative disorders are characterized by the accumulation of 8-oxo-7,8-dihydroguanine (8-oxodG) in the DNA of affected neurons. This can occur either through direct oxidation of...

Crystallization and preliminary X-ray analysis of human MTH1 complexed with two oxidized nucleotides, 8-oxo-dGMP and 2-oxo-dATP

Nakamura, Teruya, Kitaguchi, Yuki, Miyazawa, Masayuki, Kamiya, Hiroyuki, Toma, Sachiko, Ikemizu, Shinji, ...

The complexes of human MTH1 with two oxidized nucleotides, 8-oxo-dGMP and 2-oxo-dATP, were crystallized. The crystals diffracted to 1.95 and 2.22 Å resolution, respectively.

Antagonistic Regulation of Cell-Matrix Adhesion by FosB and ΔFosB/Δ2ΔFosB Encoded by Alternatively Spliced Forms of fosB Transcripts

Ohnishi, Yoshinori N., Sakumi, Kunihiko, Yamazaki, Katsuhisa, Ohnishi, Yoko H., Miura, Tomofumi, Tominaga, Yohei, ...

Among fos family genes encoding components of activator protein-1 complex, only the fosB gene produces two forms of mature transcripts, namely fosB and ΔfosB mRNAs, by alternative splicing of an...

Two distinct pathways of cell death triggered by oxidative damage to nuclear and mitochondrial DNAs

Oka, Sugako, Ohno, Mizuki, Tsuchimoto, Daisuke, Sakumi, Kunihiko, Furuichi, Masato, Nakabeppu, Yusaku

Oxidative base lesions, such as 8-oxoguanine (8-oxoG), accumulate in nuclear and mitochondrial DNAs under oxidative stress, resulting in cell death. However, it is not known which form of DNA is...

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

Fujita, Kyota, Seike, Toshihiro, Yutsudo, Noriko, Ohno, Mizuki, Yamada, Hidetaka, Yamaguchi, Hiroo, ...

It has been shown that molecular hydrogen (H2) acts as a therapeutic antioxidant and suppresses brain injury by buffering the effects of oxidative stress. Chronic oxidative stress causes...