Azathioprine and UVA Light generate mutagenic oxidative DNA damage (2005)
O'Donovan, Peter, Perrett, Conal M., Zhang, Xiaohong, Montaner, Beatriz, Xu, Yao-Zhong, Harwood, Catherine A., ...
Oxidative stress and mutagenic DNA lesions formed by reactive oxygen species (ROS) are linked to human malignancy. Clinical treatments inducing chronic oxidative stress may therefore carry a risk of...
Shigeko Morimoto, Takeshi Kato, Masamitsu Honma, Makoto Hayashi, Fumio Hanaoka, Fumio Yatagai
Morimoto, S., Kato, T., Honma, M., Hayashi, M., Hanaoka, F. and Yatagai, F. Detection of Genetic Alterations Induced by Low-Dose X Rays: Analysis of Loss of Heterozygosity for TK Mutation in Human...
Sakamoto, Aiji, Ono, Kageyoshi, Abe, Makoto, Jasmin, Gaëten, Eki, Toshihiko, Murakami, Yasufumi, ...
Cardiomyopathy (CM) is a primary degenerative disease of myocardium and is traditionally categorized into hypertrophic and dilated CMs (HCM and DCM) according to its gross appearance. Cardiomyopathic...
Molecular Architecture of the Mouse DNA Polymerase α-Primase Complex
Mizuno, Takeshi, Yamagishi, Kumiko, Miyazawa, Hiroshi, Hanaoka, Fumio
The DNA polymerase α-primase complex is the only enzyme that provides RNA-DNA primers for chromosomal DNA replication in eukaryotes. Mouse DNA polymerase α has been shown to consist of four...
Yamamoto, Seiji, Watanabe, Yoshinori, Van Der Spek, Peter J., Watanabe, Tomomichi, Fujimoto, Hiroyuki, Hanaoka, Fumio, ...
The general transcription factor TFIIE plays important roles in transcription initiation and in the transition to elongation. However, little is known about its function during these steps. Here we...
Boudsocq, François, Iwai, Shigenori, Hanaoka, Fumio, Woodgate, Roger
Phylogenetic analysis of Y-family DNA polymerases suggests that it can be subdivided into several discrete branches consisting of UmuC/DinB/Rev1/Rad30/Rad30A and Rad30B. The most diverse is the DinB...
Yamada, Ayumi, Masutani, Chikahide, Iwai, Shigenori, Hanaoka, Fumio
Defects in the human gene XPV result in the variant form of the genetic disease xeroderma pigmentosum (XP-V). XPV encodes DNA polymerase η, a novel DNA polymerase that belongs to the UmuC/DinB/Rad30...
Nishikawa, Naoko S., Izumi, Masako, Uchida, Hiroshi, Yokoi, Masayuki, Miyazawa, Hiroshi, Hanaoka, Fumio
We have isolated and determined the structure of the gene encoding the 68 kDa subunit (p68) of the mouse DNA polymerase α–primase complex. The p68 gene consists of four exons and the p68 promoter...
Mizuno, Takeshi, Ito, Nobutoshi, Yokoi, Masayuki, Kobayashi, Akio, Tamai, Katsuyuki, Miyazawa, Hiroshi, ...
DNA polymerase α-primase is a replication enzyme necessary for DNA replication in all eukaryotes examined so far. Mouse DNA polymerase α is made up of four subunits, the largest of which is the...
Izumi, Masako, Yanagi, Ken-ichiro, Mizuno, Takeshi, Yokoi, Masayuki, Kawasaki, Yasuo, Moon, Kyeong-Yeop, ...
Mcm10 (Dna43), first identified in Saccharomyces cerevisiae, is an essential protein which functions in the initiation of DNA synthesis. Mcm10 is a nuclear protein that is localized to replication...
Molecular analysis of mutations in DNA polymerase η in xeroderma pigmentosum-variant patients
Broughton, Bernard C., Cordonnier, Agnes, Kleijer, Wim J., Jaspers, Nicolaas G. J., Fawcett, Heather, Raams, Anja, ...
Xeroderma pigmentosum variant (XP-V) cells are deficient in their ability to synthesize intact daughter DNA strands after UV irradiation. This deficiency results from mutations in the gene encoding...
Ura, Kiyoe, Araki, Marito, Saeki, Hideaki, Masutani, Chikahide, Ito, Takashi, Iwai, Shigenori, ...
To investigate the relationship between chromatin dynamics and nucleotide excision repair (NER), we have examined the effect of chromatin structure on the formation of two major classes of UV-induced...
Pavlov, Youri I., Rogozin, Igor B., Galkin, Alexey P., Aksenova, Anna Y., Hanaoka, Fumio, Rada, Christina, ...
To test the hypothesis that inaccurate DNA synthesis by mammalian DNA polymerase η (pol η) contributes to somatic hypermutation (SHM) of Ig genes, we measured the error specificity of mouse pol η...
Developmental Defects and Male Sterility in Mice Lacking the Ubiquitin-Like DNA Repair Gene mHR23B
Ng, Jessica M. Y., Vrieling, Harry, Sugasawa, Kaoru, Ooms, Marja P., Grootegoed, J. Anton, Vreeburg, Jan T. M., ...
mHR23B encodes one of the two mammalian homologs of Saccharomyces cerevisiae RAD23, a ubiquitin-like fusion protein involved in nucleotide excision repair (NER). Part of mHR23B is complexed with the...
Shimizu, Yuichiro, Iwai, Shigenori, Hanaoka, Fumio, Sugasawa, Kaoru
The XPC–HR23B complex recognizes various helix-distorting lesions in DNA and initiates global genome nucleotide excision repair. Here we describe a novel functional interaction between XPC–HR23B...
Watanabe, Tomomichi, Hayashi, Kazuhiro, Tanaka, Aki, Furumoto, Tadashi, Hanaoka, Fumio, Ohkuma, Yoshiaki
The general transcription factor TFIIE plays essential roles in both transcription initiation and the transition from initiation to elongation. Previously, we systematically deleted the structural...
Mechanisms of accurate translesion synthesis by human DNA polymerase η
Masutani, Chikahide, Kusumoto, Rika, Iwai, Shigenori, Hanaoka, Fumio
The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase η (pol η), which is involved in the replication of damaged DNA. Pol η catalyzes efficient and accurate translesion...
The comings and goings of nucleotide excision repair factors on damaged DNA
Riedl, Thilo, Hanaoka, Fumio, Egly, Jean-Marc
To understand the mechanism of nucleotide excision repair (NER), one of the major human DNA repair pathways, we have set up a DNA repair system in which a linear damaged DNA substrate is immobilized...
Thymine-rich single-stranded DNA activates Mcm4/6/7 helicase on Y-fork and bubble-like substrates
You, Zhiying, Ishimi, Yukio, Mizuno, Takeshi, Sugasawa, Kaoru, Hanaoka, Fumio, Masai, Hisao
The presence of multiple clusters of runs of asymmetric adenine or thymine is a feature commonly found in eukaryotic replication origins. Here we report that the helicase and ATPase activities of the...
Jałoszyński, Paweł, Masutani, Chikahide, Hanaoka, Fumio, Perez, Ana Blanco, Nishimura, Susumu
Mutations in particular codons of c-Ha-ras have a strong activating potential, and an activated ras oncogene has been found in a number of human cancers. Using fragments of the human c-Ha-ras gene...
Misinsertion and bypass of thymine–thymine dimers by human DNA polymerase ι
Tissier, Agnès, Frank, Ekaterina G., McDonald, John P., Iwai, Shigenori, Hanaoka, Fumio, Woodgate, Roger
Human DNA polymerase ι (polι) is a recently discovered enzyme that exhibits extremely low fidelity on undamaged DNA templates. Here, we show that polι is able to facilitate limited translesion...
Structure of the central core domain of TFIIEβ with a novel double-stranded DNA-binding surface
Okuda, Masahiko, Watanabe, Yoshinori, Okamura, Hideyasu, Hanaoka, Fumio, Ohkuma, Yoshiaki, Nishimura, Yoshifumi
Human general transcription factor TFIIE consists of two subunits, TFIIEα and TFIIEβ. Recently, TFIIEβ has been found to bind to the region where the promoter starts to open to be single-stranded...
Error-prone bypass of certain DNA lesions by the human DNA polymerase κ
Ohashi, Eiji, Ogi, Tomoo, Kusumoto, Rika, Iwai, Shigenori, Masutani, Chikahide, Hanaoka, Fumio, ...
The Escherichia coli protein DinB is a newly identified error-prone DNA polymerase. Recently, a human homolog of DinB was identified and named DINB1. We report that the DINB1 gene encodes a DNA...
Palm Mutants in DNA Polymerases α and η Alter DNA Replication Fidelity and Translesion Activity
Niimi, Atsuko, Limsirichaikul, Siripan, Yoshida, Shonen, Iwai, Shigenori, Masutani, Chikahide, Hanaoka, Fumio, ...
We isolated active mutants in Saccharomyces cerevisiae DNA polymerase α that were associated with a defect in error discrimination. Among them, L868F DNA polymerase α has a spontaneous error...
Chemical synthesis and translesion replication of a cis–syn cyclobutane thymine–uracil dimer
Takasawa, Kohei, Masutani, Chikahide, Hanaoka, Fumio, Iwai, Shigenori
The cytosine base in DNA undergoes hydrolytic deamination at a considerable rate when UV radiation induces formation of a cyclobutane pyrimidine dimer (CPD) with an adjacent pyrimidine base. We have...
Martomo, Stella A., Yang, William W., Wersto, Robert P., Ohkumo, Tsuyoshi, Kondo, Yuji, Yokoi, Masayuki, ...
Hypermutation in immunoglobulin genes produces a high frequency of substitutions of all four bases, which are likely generated by low-fidelity DNA polymerases. Indeed, humans deficient for DNA...
Nishi, Ryotaro, Okuda, Yuki, Watanabe, Eriko, Mori, Toshio, Iwai, Shigenori, Masutani, Chikahide, ...
Xeroderma pigmentosum group C (XPC) protein plays a key role in DNA damage recognition in global genome nucleotide excision repair (NER). The protein forms in vivo a heterotrimeric complex involving...
Erroneous incorporation of oxidized DNA precursors by Y-family DNA polymerases
Shimizu, Masatomi, Gruz, Petr, Kamiya, Hiroyuki, Kim, Su-Ryang, Pisani, Francesca M., Masutani, Chikahide, ...
Deranged oxidative metabolism is a property of many tumour cells. Oxidation of the deoxynucleotide triphosphate (dNTP) pool, as well as DNA, is a major cause of genome instability. Here, we report...
Nakamura, Mirai, Nabetani, Akira, Mizuno, Takeshi, Hanaoka, Fumio, Ishikawa, Fuyuki
Telomere length is controlled by a homeostatic mechanism that involves telomerase, telomere-associated proteins, and conventional replication machinery. Specifically, the coordinated actions of the...
Kannouche, Patricia, Broughton, Bernard C., Volker, Marcel, Hanaoka, Fumio, Mullenders, Leon H.F., Lehmann, Alan R.
DNA polymerase η carries out translesion synthesis past UV photoproducts and is deficient in xeroderma pigmentosum (XP) variants. We report that polη is mostly localized uniformly in the nucleus...
A multistep damage recognition mechanism for global genomic nucleotide excision repair
Sugasawa, Kaoru, Okamoto, Tomoko, Shimizu, Yuichiro, Masutani, Chikahide, Iwai, Shigenori, Hanaoka, Fumio
A mammalian nucleotide excision repair (NER) factor, the XPC–HR23B complex, can specifically bind to certain DNA lesions and initiate the cell-free repair reaction. Here we describe a detailed...
Sakamoto, Aiji, Ono, Kageyoshi, Abe, Makoto, Jasmin, Gaëten, Eki, Toshihiko, Murakami, Yasufumi, ...
Cardiomyopathy (CM) is a primary degenerative disease of myocardium and is traditionally categorized into hypertrophic and dilated CMs (HCM and DCM) according to its gross appearance. Cardiomyopathic...
Molecular Architecture of the Mouse DNA Polymerase α-Primase Complex
Mizuno, Takeshi, Yamagishi, Kumiko, Miyazawa, Hiroshi, Hanaoka, Fumio
The DNA polymerase α-primase complex is the only enzyme that provides RNA-DNA primers for chromosomal DNA replication in eukaryotes. Mouse DNA polymerase α has been shown to consist of four...
Yamamoto, Seiji, Watanabe, Yoshinori, Van Der Spek, Peter J., Watanabe, Tomomichi, Fujimoto, Hiroyuki, Hanaoka, Fumio, ...
The general transcription factor TFIIE plays important roles in transcription initiation and in the transition to elongation. However, little is known about its function during these steps. Here we...
Boudsocq, François, Iwai, Shigenori, Hanaoka, Fumio, Woodgate, Roger
Phylogenetic analysis of Y-family DNA polymerases suggests that it can be subdivided into several discrete branches consisting of UmuC/DinB/Rev1/Rad30/Rad30A and Rad30B. The most diverse is the DinB...
Yamada, Ayumi, Masutani, Chikahide, Iwai, Shigenori, Hanaoka, Fumio
Defects in the human gene XPV result in the variant form of the genetic disease xeroderma pigmentosum (XP-V). XPV encodes DNA polymerase η, a novel DNA polymerase that belongs to the UmuC/DinB/Rad30...
Nishikawa, Naoko S., Izumi, Masako, Uchida, Hiroshi, Yokoi, Masayuki, Miyazawa, Hiroshi, Hanaoka, Fumio
We have isolated and determined the structure of the gene encoding the 68 kDa subunit (p68) of the mouse DNA polymerase α–primase complex. The p68 gene consists of four exons and the p68 promoter...
Mizuno, Takeshi, Ito, Nobutoshi, Yokoi, Masayuki, Kobayashi, Akio, Tamai, Katsuyuki, Miyazawa, Hiroshi, ...
DNA polymerase α-primase is a replication enzyme necessary for DNA replication in all eukaryotes examined so far. Mouse DNA polymerase α is made up of four subunits, the largest of which is the...
Izumi, Masako, Yanagi, Ken-ichiro, Mizuno, Takeshi, Yokoi, Masayuki, Kawasaki, Yasuo, Moon, Kyeong-Yeop, ...
Mcm10 (Dna43), first identified in Saccharomyces cerevisiae, is an essential protein which functions in the initiation of DNA synthesis. Mcm10 is a nuclear protein that is localized to replication...
Molecular analysis of mutations in DNA polymerase η in xeroderma pigmentosum-variant patients
Broughton, Bernard C., Cordonnier, Agnes, Kleijer, Wim J., Jaspers, Nicolaas G. J., Fawcett, Heather, Raams, Anja, ...
Xeroderma pigmentosum variant (XP-V) cells are deficient in their ability to synthesize intact daughter DNA strands after UV irradiation. This deficiency results from mutations in the gene encoding...
Ura, Kiyoe, Araki, Marito, Saeki, Hideaki, Masutani, Chikahide, Ito, Takashi, Iwai, Shigenori, ...
To investigate the relationship between chromatin dynamics and nucleotide excision repair (NER), we have examined the effect of chromatin structure on the formation of two major classes of UV-induced...
Pavlov, Youri I., Rogozin, Igor B., Galkin, Alexey P., Aksenova, Anna Y., Hanaoka, Fumio, Rada, Christina, ...
To test the hypothesis that inaccurate DNA synthesis by mammalian DNA polymerase η (pol η) contributes to somatic hypermutation (SHM) of Ig genes, we measured the error specificity of mouse pol η...
Developmental Defects and Male Sterility in Mice Lacking the Ubiquitin-Like DNA Repair Gene mHR23B
Ng, Jessica M. Y., Vrieling, Harry, Sugasawa, Kaoru, Ooms, Marja P., Grootegoed, J. Anton, Vreeburg, Jan T. M., ...
mHR23B encodes one of the two mammalian homologs of Saccharomyces cerevisiae RAD23, a ubiquitin-like fusion protein involved in nucleotide excision repair (NER). Part of mHR23B is complexed with the...
Shimizu, Yuichiro, Iwai, Shigenori, Hanaoka, Fumio, Sugasawa, Kaoru
The XPC–HR23B complex recognizes various helix-distorting lesions in DNA and initiates global genome nucleotide excision repair. Here we describe a novel functional interaction between XPC–HR23B...
Watanabe, Tomomichi, Hayashi, Kazuhiro, Tanaka, Aki, Furumoto, Tadashi, Hanaoka, Fumio, Ohkuma, Yoshiaki
The general transcription factor TFIIE plays essential roles in both transcription initiation and the transition from initiation to elongation. Previously, we systematically deleted the structural...
Mechanisms of accurate translesion synthesis by human DNA polymerase η
Masutani, Chikahide, Kusumoto, Rika, Iwai, Shigenori, Hanaoka, Fumio
The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase η (pol η), which is involved in the replication of damaged DNA. Pol η catalyzes efficient and accurate translesion...
The comings and goings of nucleotide excision repair factors on damaged DNA
Riedl, Thilo, Hanaoka, Fumio, Egly, Jean-Marc
To understand the mechanism of nucleotide excision repair (NER), one of the major human DNA repair pathways, we have set up a DNA repair system in which a linear damaged DNA substrate is immobilized...
Thymine-rich single-stranded DNA activates Mcm4/6/7 helicase on Y-fork and bubble-like substrates
You, Zhiying, Ishimi, Yukio, Mizuno, Takeshi, Sugasawa, Kaoru, Hanaoka, Fumio, Masai, Hisao
The presence of multiple clusters of runs of asymmetric adenine or thymine is a feature commonly found in eukaryotic replication origins. Here we report that the helicase and ATPase activities of the...
Jałoszyński, Paweł, Masutani, Chikahide, Hanaoka, Fumio, Perez, Ana Blanco, Nishimura, Susumu
Mutations in particular codons of c-Ha-ras have a strong activating potential, and an activated ras oncogene has been found in a number of human cancers. Using fragments of the human c-Ha-ras gene...
Misinsertion and bypass of thymine–thymine dimers by human DNA polymerase ι
Tissier, Agnès, Frank, Ekaterina G., McDonald, John P., Iwai, Shigenori, Hanaoka, Fumio, Woodgate, Roger
Human DNA polymerase ι (polι) is a recently discovered enzyme that exhibits extremely low fidelity on undamaged DNA templates. Here, we show that polι is able to facilitate limited translesion...
Structure of the central core domain of TFIIEβ with a novel double-stranded DNA-binding surface
Okuda, Masahiko, Watanabe, Yoshinori, Okamura, Hideyasu, Hanaoka, Fumio, Ohkuma, Yoshiaki, Nishimura, Yoshifumi
Human general transcription factor TFIIE consists of two subunits, TFIIEα and TFIIEβ. Recently, TFIIEβ has been found to bind to the region where the promoter starts to open to be single-stranded...
Kannouche, Patricia, Broughton, Bernard C., Volker, Marcel, Hanaoka, Fumio, Mullenders, Leon H.F., Lehmann, Alan R.
DNA polymerase η carries out translesion synthesis past UV photoproducts and is deficient in xeroderma pigmentosum (XP) variants. We report that polη is mostly localized uniformly in the nucleus...
A multistep damage recognition mechanism for global genomic nucleotide excision repair
Sugasawa, Kaoru, Okamoto, Tomoko, Shimizu, Yuichiro, Masutani, Chikahide, Iwai, Shigenori, Hanaoka, Fumio
A mammalian nucleotide excision repair (NER) factor, the XPC–HR23B complex, can specifically bind to certain DNA lesions and initiate the cell-free repair reaction. Here we describe a detailed...
Error-prone bypass of certain DNA lesions by the human DNA polymerase κ
Ohashi, Eiji, Ogi, Tomoo, Kusumoto, Rika, Iwai, Shigenori, Masutani, Chikahide, Hanaoka, Fumio, ...
The Escherichia coli protein DinB is a newly identified error-prone DNA polymerase. Recently, a human homolog of DinB was identified and named DINB1. We report that the DINB1 gene encodes a DNA...
Palm Mutants in DNA Polymerases α and η Alter DNA Replication Fidelity and Translesion Activity
Niimi, Atsuko, Limsirichaikul, Siripan, Yoshida, Shonen, Iwai, Shigenori, Masutani, Chikahide, Hanaoka, Fumio, ...
We isolated active mutants in Saccharomyces cerevisiae DNA polymerase α that were associated with a defect in error discrimination. Among them, L868F DNA polymerase α has a spontaneous error...
Chemical synthesis and translesion replication of a cis–syn cyclobutane thymine–uracil dimer
Takasawa, Kohei, Masutani, Chikahide, Hanaoka, Fumio, Iwai, Shigenori
The cytosine base in DNA undergoes hydrolytic deamination at a considerable rate when UV radiation induces formation of a cyclobutane pyrimidine dimer (CPD) with an adjacent pyrimidine base. We have...
Martomo, Stella A., Yang, William W., Wersto, Robert P., Ohkumo, Tsuyoshi, Kondo, Yuji, Yokoi, Masayuki, ...
Hypermutation in immunoglobulin genes produces a high frequency of substitutions of all four bases, which are likely generated by low-fidelity DNA polymerases. Indeed, humans deficient for DNA...
Nishi, Ryotaro, Okuda, Yuki, Watanabe, Eriko, Mori, Toshio, Iwai, Shigenori, Masutani, Chikahide, ...
Xeroderma pigmentosum group C (XPC) protein plays a key role in DNA damage recognition in global genome nucleotide excision repair (NER). The protein forms in vivo a heterotrimeric complex involving...
Erroneous incorporation of oxidized DNA precursors by Y-family DNA polymerases
Shimizu, Masatomi, Gruz, Petr, Kamiya, Hiroyuki, Kim, Su-Ryang, Pisani, Francesca M., Masutani, Chikahide, ...
Deranged oxidative metabolism is a property of many tumour cells. Oxidation of the deoxynucleotide triphosphate (dNTP) pool, as well as DNA, is a major cause of genome instability. Here, we report...