Laboratory of biophysics and biochemistry, Department of Chemistry, Graduate School of Science and Engineering, Tokyo Metropolitan University




Tsuda M, Terada K, Ooka M, Kobayashi K, Sasanuma H, Fujisawa R, Tsurimoto T, Yamamoto J, Iwai S, Kadoda K, Akagawa R, Huang SN, Pommier Y, Sale JE, Takeda S, Hirota K. (2017) The dominant role of proofreading exonuclease activity of replicative polymerase ε in cellular tolerance to cytarabine (Ara-C). Oncotarget. (in press) doi: 10.18632/oncotarget.16508.
Fujisawa R, Ohashi E, Hirota K, Tsurimoto T. (2017) Human CTF18-RFC clamp-loader complexed with non-synthesising DNA polymerase ε efficiently loads the PCNA sliding clamp.Nucleic Acids Res. (in press) doi: 10.1093/nar/gkx096. 


Ooka M,  Kobayashi K, Abe T, Akiyama K, Hada M, Takeda S and Hirota K (2016) Determination of genotoxic potential by comparison of structurally related azo dyes using DNA repair-deficient DT40 mutant panels Chemosphere 164:106-112. doi: 10.1016/j.chemosphere.
Yamamoto J. Takahata C, Kuraoka I, Hirota K, Iwai S.(2016) Chemical Incorporation of Chain-Terminating Nucleoside Analogs as 3’-Blocking DNA Damage and Their Removal by Human ERCC1-XPF Endonuclease Molecules 21(6). pii: E766. doi: 10.3390/molecules21060766.
Kobayashi K, Guilliam TA, Tsuda M, Yamamoto J, Bailey LJ, Iwai S, Takeda S, Doherty AJ, Hirota K.Repriming by PrimPol is critical for DNA replication restart downstream of lesions and chain-terminating nucleosides. Cell Cycle 2016 May 26:0. [Epub ahead of print]
Hirota K, Tsuda M, Mohiuddin, Tsurimoto T, Cohen IS, Livneh Z, Kobayashi K, Narita T, Nishihara K, Murai J, Iwai S, Guilbaud G, Sale JE, Takeda S. In vivo evidence for translesion synthesis by the replicative DNA polymerase δ.Nucleic Acids Res. 2016 May 16. pii: gkw439. [Epub ahead of print]
Takemata N, Oda A, Yamada T, Galipon J, Miyoshi T, Suzuki Y, Sugano S, Hoffman CS, Hirota K, Ohta K. Local potentiation of stress-responsive genes by upstream noncoding transcription. Nucleic Acids Res. 2016 Mar 3. pii: gkw142. [Epub ahead of print]


Tada K, Kobayashi M, Takiuchi Y, Iwai F, Sakamoto T, Nagata K, Shinohara M, Io K, Shirakawa K, Hishizawa M, Shindo K, Kadowaki N, Hirota K, Yamamoto J, Iwai S, Sasanuma H, Takeda S, Takaori-Kondo A. Abacavir, an anti-HIV-1 drug, targets TDP1-deficient adult T cell leukemia. Sci Adv. 2015 Apr 24;1(3):e1400203.
Hoa NN, Akagawa R, Yamasaki T, Hirota K, Sasa K, Natsume T, Kobayashi J, Sakuma T, Yamamoto T, Komatsu K, Kanemaki MT, Pommier Y, Takeda S, Sasanuma H. Relative contribution of four nucleases, CtIP, Dna2, Exo1 and Mre11, to the initial step of DNA double-strand break repair by homologous recombination in both the chicken DT40 and human TK6 cell lines. Genes Cells. 2015 20, 1059-1076
Ooka, M., Takazawa, H., Takeda, S., and Hirota, K. Cytotoxic and genotoxic profiles of benzo[a]pyrene and N-nitrosodimethylamine demonstrated using DNA repair deficient DT40 cells with metabolic activation. Chemosphere (in press)
Shimizu, N., Ooka, M., Takagi, T., Takeda, S., Hirota, K.Distinct DNA damage spectra induced by ionizing radiation in normoxic and hypoxic cells. Radiation Res. 183,442-8 
Kobayashi, K., Fujii, T., Asada, R., Ooka, M., and Hirota, K. Development of a targeted flip-in system in avian DT40 cells. PLoS One 10, e0122006.(2015).
Hirota, K., Yoshikiyo, K., Guilbaud, G., Tsurimoto, T., Murai, J., Tsuda, M., Phillips, L., Narita, T., Nishihara, K., Kobayashi, K., Yamada, K., Nakamura, J., Pommier, Y., Lehmann, A., Sale, J., and Takeda, S.,The POLD3 subunit of DNA polymerase δ can promote translesion synthesis independently of DNA polymerase ζ 2015 Nucleic Acids Res 43(3):1671-83.
Kobayashi, S., Kasaishi, Y., Nakada, S., Takagi, T., Era, S., Motegi, A., Chiu, R.K., Takeda, S., and Hirota, K. Rad18 and Rnf8 facilitate homologous recombination by two distinct mechanisms, promoting Rad51 focus formation and suppressing the toxic effect of nonhomologous end joining. 2015. Oncogene in press
Asada, R., Takemata, N., Hoffman, C.S., Ohta, K., and Hirota, K. Antagonistic controls of chromatin and mRNA start site selection by Tup family corepressors and the CCAAT-binding factor. 2015 Mol Cell Biol 35(5):847-55.   


Hirota, K., Tsuda, M., Murai, J., Takagi, T., Keka, I.S., Narita, T., Fujita, M., Sasanuma, H., Kobayashi, J., and Takeda, S. (2014). SUMO-targeted ubiquitin ligase RNF4 plays a critical role in preventing chromosome loss. Genes Cells 19, 743-754.
Sabouri S, Kobayashi M, Begum NA, Xu J, Hirota K, Honjo T. C-terminal region of activation-induced cytidine deaminase (AID) is required for efficient class switch recombination and gene conversion. Proc Natl Acad Sci U S A. 2014 111(6):2253-8
Al Abo M, Dejsuphong D, Hirota K, Yonetani Y, Yamazoe M, Kurumizaka H, Takeda S. Compensatory functions and interdependency of the DNA-binding domain of BRCA2 with the BRCA1-PALB2-BRCA2 complex. Cancer Res. 2014 74(3):797-807. 
Mohiuddin, I. S. Keka, T. J. Evans, K. Hirota, H. Shimizu, K. Kono, S. Takeda, S. Hirano A novel genotoxicity assay of carbon nanotubes using functional macrophage receptor with collagenous structure (MARCO)-expressing chicken B lymphocytes. Arch Toxicol. 2014 88(1):145-60.
Yamamoto, K.N., Hirota, K., Takeda, S., and Haeno, H. Evolution of pre-existing versus acquired resistance to platinum drugs and PARP inhibitors in BRCA-associated cancers. (2014).  PLoS One 9, e105724.


Kikuchi, K, Narita, T., Van, P.T., Iijima, J., Hirota, K., Keka, I.S.,Mohiuddin, Okawa, K., Hori, T., Fukagawa, T., Essers, J., Kanaar, R.,Whitby, M.C., Sugasawa, K., Taniguchi, Y., Kitagawa, K., and Takeda, S. Structure-specific endonucleases Xpf and Mus81 play overlapping but essential roles in DNA repair by homologous recombination. Cancer Research Jul 15;73(14):4362-4371.(2013).
Y. Saito, J. Takeda, M. Okada, J. Kobayashi, A. Kato, K. Hirota, M. Taoka, T. Matsumoto, K. Komatsu and T. Isobe. The proteasome factor Bag101 binds to Rad22 and suppresses homologous recombination. Sci Rep 3, 2022. (2013).
Fujita M, Sasanuma H, Yamamoto K.N, Harada H, Kurosawa A, Adachi N, Omura M, Hiraoka M, Takeda S, Hirota K. Interference in DNA replication can cause mitotic chromosomal breakage unassociated with double-strand breaks [[PLOS ONE>]] (2013)


Miyoshi T, Ito M, Kugou K, Yamada S, Furuichi M, Oda A, Yamada T, Hirota K, Masai H, Ohta K. A Central Coupler for Recombination Initiation Linking Chromosome Architecture to S Phase Checkpoint. [[Mol. Cell>]] 47(5):722-33 (2012)


J. Murai, K. Yang, D. Dejsuphong, K. Hirota, S. Takeda and A. D. D'Andrea The USP1/UAF1 Complex Promotes Double-Strand Break Repair through Homologous Recombination. Molecular and cellular biology 31, 2462-2469 (2011).
Y. Qing, M. Yamazoe, K. Hirota, D. Dejsuphong, W. Sakai, K. N. Yamamoto, D. K. Bishop, X. Wu and S. Takeda, The Epistatic Relationship between BRCA2 and the Other RAD51 Mediators in Homologous Recombination.  PLoS genetics 7, e1002148 (2011).
K. N. Yamamoto, K. Hirota, K. Kono, S. Takeda, S. Sakamuru, M. Xia, R. Huang, C. P. Austin, K. L. Witt and R. R. Tice, Characterization of environmental chemicals with potential for DNA damage using isogenic DNA repair-deficient chicken DT40 cell lines. Environmental and molecular mutagenesis (2011).
K. N. Yamamoto, S. Kobayashi, M. Tsuda, H. Kurumizaka, M. Takata, K. Kono, J. Jiricny, S. Takeda and K. Hirota, Involvement of SLX4 in interstrand cross-link repair is regulated by the Fanconi anemia pathway. [[Proceedings of the National Academy of Sciences of the United States of America>]] 108, 6492-6496 (2011).
Takaku M, Tsujita T, Horikoshi N, Takizawa Y, Qing Y, Hirota K, Ikura M, Ikura T, Takeda S, Kurumizaka H. Purification of the human SMN-GEMIN2 complex and assessment of its stimulation of RAD51-mediated DNA recombination reactions. Biochemistry 32, 6797-6805 (2011).


T. J. Evans, K. N. Yamamoto, K. Hirota and S. Takeda, Mutant cells defective in DNA repair pathways provide a sensitive high-throughput assay for genotoxicity.DNA repair 9, 1292-1298 (2010).
K. Hirota, E. Sonoda, T. Kawamoto, A. Motegi, C. Masutani, F. Hanaoka, D. Szuts, S. Iwai, J. E. Sale, A. Lehmann and S. Takeda, Simultaneous disruption of two DNA polymerases, Poleta and Polzeta, in Avian DT40 cells unmasks the role of Poleta in cellular response to various DNA lesions. [[PLoS genetics>]] 6, (2010).
M. Kohzaki, K. Nishihara, K. Hirota, E. Sonoda, M. Yoshimura, S. Ekino, J. E. Butler, M. Watanabe, T. D. Halazonetis and S. Takeda, DNA polymerases nu and theta are required for efficient immunoglobulin V gene diversification in chicken. The Journal of cell biology 189, 1117-1127 (2010).
T. Narita, T. Tsurimoto, J. Yamamoto, K. Nishihara, K. Ogawa, E. Ohashi, T. Evans, S. Iwai, S. Takeda and K. Hirota, Human replicative DNA polymerase delta can bypass T-T (6-4) ultraviolet photoproducts on template strands.[[Genes Cells>]] 15, 1228-1239 (2010).
N. Nemoto, T. Udagawa, T. Ohira, L. Jiang, K. Hirota, C. R. Wilkinson, J. Bahler, N. Jones, K. Ohta, R. C. Wek and K. Asano, The roles of stress-activated Sty1 and Gcn2 kinases and of the protooncoprotein homologue Int6/eIF3e in responses to endogenous oxidative stress during histidine starvation. Journal of molecular biology 404, 183-201 (2010).
Y. Takizawa, Y. Qing, M. Takaku, T. Ishida, Y. Morozumi, T. Tsujita, T. Kogame, K. Hirota, M. Takahashi, T. Shibata, H. Kurumizaka and S. Takeda, GEMIN2 promotes accumulation of RAD51 at double-strand breaks in homologous recombination. Nucleic acids research, (2010).
K. Yoshikiyo, K. Kratz, K. Hirota, K. Nishihara, M. Takata, H. Kurumizaka, S. Horimoto, S. Takeda and J. Jiricny, KIAA1018/FAN1 nuclease protects cells against genomic instability induced by interstrand cross-linking agents. Proceedings of the National Academy of Sciences of the United States of America 107, 21553-21557 (2010).


Analysis of chromatin structure at meiotic DSB sites in yeasts. K. Hirota, T. Fukuda, T. Yamada and K. Ohta, Methods in molecular biology (Clifton, N.J 557, 253-266 (2009).
Cascade transcription of mRNA-type long non-coding RNAs (mlonRNAs) and local chromatin remodeling. K. Hirota and K. Ohta, Epigenetics 4, 5-7 (2009).
Transcription of mRNA-type long non-coding RNAs (mlonRNAs) disrupts chromatin array. K. Hirota and K. Ohta, Communicative & Integrative Biology 2, 25-26 (2009).
Bloom DNA helicase facilitates homologous recombination between diverged homologous sequences. K. Kikuchi, H. I. Abdel-Aziz, Y. Taniguchi, M. Yamazoe, S. Takeda and K. Hirota, [[The Journal of biological chemistry>]] 284, 26360-26367 (2009).
In-cell Viscosity Measurement Using a Fluorescence Up-conversion Microscope. . T. Fujino, K. Hirota, K. Ohta and T. Tahara, Chemistry Letters 37, 1240 (2008).
Structural and functional analyses of the DMC1-M200V polymorphism found in the human population. J. Hikiba, K. Hirota, W. Kagawa, S. Ikawa, T. Kinebuchi, I. Sakane, Y. Takizawa, S. Yokoyama, B. Mandon-Pepin, A. Nicolas, T. Shibata, K. Ohta and H. Kurumizaka, Nucleic acids research 36, 4181-4190 (2008).
Stepwise chromatin remodelling by a cascade of transcription initiation of non-coding RNAs. K. Hirota, T. Miyoshi, K. Kugou, C. S. Hoffman, T. Shibata and K. Ohta, [[Nature>]] 456, 130-134 (2008).
Distinct chromatin modulators regulate the formation of accessible and repressive chromatin at the fission yeast recombination hotspot ade6-M26. K. Hirota, K. Mizuno, T. Shibata and K. Ohta, [[Molecular biology of the cell>]] 19, 1162-1173 (2008).
Cdc7-dependent phosphorylation of Mer2 facilitates initiation of yeast meiotic recombination. H. Sasanuma, K. Hirota, T. Fukuda, N. Kakusho, K. Kugou, Y. Kawasaki, T. Shibata, H. Masai and K. Ohta, Genes & development 22, 398-410 (2008).
Essential roles of Snf21, a Swi2/Snf2 family chromatin remodeler, in fission yeast mitosis. K. Yamada, K. Hirota, K. Mizuno, T. Shibata and K. Ohta, Genes & genetic systems 83, 361-372 (2008).
Multiple modes of chromatin configuration at natural meiotic recombination hot spots in fission yeast. K. Hirota, W. W. Steiner, T. Shibata and K. Ohta, Eukaryotic cell 6, 2072-2080 (2007).
K. Hirota, C. S. Hoffman and K. Ohta. Reciprocal nuclear shuttling of two antagonizing Zn finger proteins modulates Tup family corepressor function to repress chromatin remodeling. Eukaryot Cell 5, 1980-9. (2006).
K. Ogino, K. Hirota, S. Matsumoto, T. Takeda, K. Ohta, K. Arai and H. Masai. Hsk1 kinase is required for induction of meiotic dsDNA breaks without involving checkpoint kinases in fission yeast. Proc Natl Acad Sci U S A 103, 8131-6. (2006).
M. K. Davidson, H. K. Shandilya, K. Hirota, K. Ohta and W. P. Wahls. Atf1-Pcr1-M26 complex links stress-activated MAPK and cAMP-dependent protein kinase pathways via chromatin remodeling of cgs2+. J Biol Chem 279, 50857-63. (2004).
K. Hirota, T. Hasemi, T. Yamada, K. I. Mizuno, C. S. Hoffman, T. Shibata and K. Ohta. Fission yeast global repressors regulate the specificity of chromatin alteration in response to distinct environmental stresses. Nucleic Acids Res 32, 855-62. (2004).
T. Yamada, K. Mizuno, K. Hirota, N. Kon, W. P. Wahls, E. Hartsuiker, H. Murofushi, T. Shibata and K. Ohta. Roles of histone acetylation and chromatin remodeling factor in a meiotic recombination hotspot. Embo J 23, 1792-803. (2004).
K. Hirota, C. S. Hoffman, T. Shibata and K. Ohta. Fission yeast Tup1-like repressors repress chromatin remodeling at the fbp1+ promoter and the ade6-M26 recombination hotspot. Genetics 165, 505-15. (2003).
K. Hirota, K. Tanaka, K. Ohta and M. Yamamoto. Gef1p and Scd1p, the Two GDP-GTP exchange factors for Cdc42p, form a ring structure that shrinks during cytokinesis in Schizosaccharomyces pombe. Mol Biol Cell 14, 3617-27. (2003).
K. Hirota, K. Tanaka, Y. Watanabe and M. Yamamoto. Functional analysis of the C-terminal cytoplasmic region of the M-factor receptor in fission yeast. Genes Cells 6, 201-14. (2001).

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