FUNCTIONAL ANALYSIS OF CANCER-SUSCEPTIBIE GENE, NBS1

2009 Fiscal Year Final Research Report

• Project/Area Number: 17013040
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyoto University
• Principal Investigator: KOMATSU Kenshi Kyoto University, 放射線生物研究センター, 教授 (80124577)
• Co-Investigator(Kenkyū-buntansha): KOBAYASHI Junya 京都大学, 放射線生物研究センター, 助教 (30301302)
• Project Period (FY): 2005 – 2009
• Keywords: DNA二重鎖切断 / NBSI,BRCAI,中心体 / 相同組換え / シスプラチン増感

Research Abstract

We showed here that NBS1 is involved in human homologous recombination. Contrast to other underlying genes of radiation sensitive genetic syndrome, such as ATM and BRCA1, NBS1 functions in early step of homologous recombination. In addition, we revealed that NBS1 binds to TOPBP1, which is an important factor for activation of ATR, and disruption of NBS1 leads to enhanced sensitivity to UV and anti-tumor drug, cis-platin. Furthermore, we showed that NBS1 has critical role in genome stability through maintaining centrosomes.

Research Products

• [Journal Article] Bisbenzamidine derivative, Pentamidine represses DNA damage response through inhibition of histone H2A acetylation. (2010)
  • Author(s): Kobayashi J, Kato A, Ota Y, Ohba R, Komatsu K.
  • Journal Title: Mol. Cancer 9 Pages: 34
  • Peer Reviewed
• [Journal Article] Two major factors involved in the reverse dose-rate effect for somatic mutation induction are the cell cycle position and LET value. (2009)
  • Author(s): Tauchi H, Waku H, Matsumoto E, Yara S, Okumura S, Iwata Y, Komatsu K, Furusawa Y, Eguchi-Kasai K, Tachibana A.
  • Journal Title: J Radiat Res 50 Pages: 441-8
  • Peer Reviewed
• [Journal Article] Histone H2AX participates the DNA damage-induced ATM activation through interaction with NBS1. (2009)
  • Author(s): Kobayashi J, Tauchi H, Chen B, Bruma S, Tashiro S, Matsuura S, Tanimoto K, Chen DJ, Komatsu K.
  • Journal Title: Biochem Biophys Res Commun. 380 Pages: 752-757
  • Peer Reviewed
• [Journal Article] DNA double strand break repair enzymes function at multiple steps in HIV-1 infection. (2009)
  • Author(s): Sakurai, Y. Komatsu, K. Agematsu, K. Matsuoka, M.
  • Journal Title: Retrovirology. 6 Pages: 114
  • Peer Reviewed
• [Journal Article] Emerging connection between centrosome and DNA Emerging repair machinery. (2009)
  • Author(s): Shimada M, Komatsu K.
  • Journal Title: J Radiat Res 50 Pages: 295-301
  • Peer Reviewed
• [Journal Article] Inactivation of the Nijmegen breakage syndrome gene NBS1 leads to excess centrosome duplication via the ATR/BRCA1 pathway. (2009)
  • Author(s): Shimada M, Sagae R, Kobayashi J, Habu T, Komatsu K.
  • Journal Title: Cancer Research 69 Pages: 1768-75
  • Peer Reviewed
• [Journal Article] NBS1 prevents chromatid-type aberrations through ATM-dependent interactions with SMC1. (2008)
  • Author(s): Antoccia A, Sakamoto S, Matsuura S, Tauchi H, Komatsu K.
  • Journal Title: Radiat Res. 170 Pages: 345-352
  • Peer Reviewed
• [Journal Article] Ono T. Absence of Ku70 gene obliterates X-ray-induced lacZ mutagenesis of small deletions in mouse tissues. (2008)
  • Author(s): Uehara Y, Ikehata H, Komura J, Ito A, Ogata M, Itoh T, Hirayama R, Furusawa Y, Ando K, Paunesku T, Woloschak GE, Komatsu K, Matsuura S, Ikura T, Kamiya K
  • Journal Title: Radiat Res. 170 Pages: 216-223
  • Peer Reviewed
• [Journal Article] Potential Link between Alternative Splicing of the NBS1 Gene and theDNA Damage/Environmental Stress. (2008)
  • Author(s): Takai K, Sakamoto S, Sakai T, Yasunaga J, Komatsu K, Matsuoka M.
  • Journal Title: Radiat Res. 170 Pages: 33-40
  • Peer Reviewed
• [Journal Article] NBS1 regulates a novel apoptotic pathway through Bax activation. (2008)
  • Author(s): Iijima K, Muranaka C, Kobayashi J, Sakamoto S, Komatsu K, Matsuura S, Kubota N, Tauchi H.
  • Journal Title: DNA Repair 7 Pages: 1705-16
  • Peer Reviewed
• [Journal Article] Impaired removal of DNA interstrand cross-link in Nijmegen breakage syndrome and Fanconi anemia, but not in BRCA-defective group. (2008)
  • Author(s): Tsuchida K., Komatsu K.
  • Journal Title: Cancer Sci. 99 Pages: 2238-43
  • Peer Reviewed
• [Journal Article] Current topics in DNA double-strand break repair. (2008)
  • Author(s): Kobayashi J, Iwabuchi K, Miyagawa K, Sonoda E, Suzuki K, Takata M, Tauchi H.
  • Journal Title: J Radiat Res 49 Pages: 93-103
  • Peer Reviewed
• [Journal Article] Homologous recombination repair is regulated by domains at the C-terminus of NBS1 and is independent of ATM. (2007)
  • Author(s): S. Sakamoto, K. Iijima, D. Mochizuki, K. Nakamura, K. Teshigawara, J. Kobayashi, S. Matsuura, H. Tauchi, K. Komatsu.
  • Journal Title: Oncogene 26 Pages: 6002-9
  • Peer Reviewed
• [Journal Article] DNA Repair Defect in AT Cells and their Ishizaki. Hypersensitivity to Low-Dose-Rate Radiation. (2006)
  • Author(s): H. Nakamura, Y. Yasui, N. Saito, A. Tachibana, K. Komatsu, Ishizaki
  • Journal Title: Radiation research. 165 Pages: 277-282
  • Peer Reviewed
• [Journal Article] Nijmegen Breakage Syndrome and Functions of the Responsible Nijmegen Breakage Protein (2006)
  • Author(s): A. Antoccia, J. Kobayashi, H. Tauchi, S. Matsuura, K. Komatsu.
  • Journal Title: NBS1. Genome Dyn. 1 Pages: 191-205
  • Peer Reviewed
• [Journal Article] ATM Activation by a Sulfhydryl-Reactive Inflammatory Cyclopentenone Prostaglandin. (2006)
  • Author(s): M. Kobayashi, H. Ono, K. Mihara, H. Tauchi, K. Komatsu, H. Shimizu, K. Uchida, K. Yamamoto.
  • Journal Title: Genes Cells 11(7) Pages: 779-789
  • Peer Reviewed
• [Journal Article] Association of Ionizing Radiation-Induced Foci of NBS1 with Association of Ionizing Chromosomal Instability and Breast Cancer Susceptibility. (2006)
  • Author(s): M. Someya, K. Sakata, H. Tauchi, Y. Matsumoto, A. Nakamura, K. Komatsu, M. Hareyama.
  • Journal Title: Radiation Research. 166 Pages: 575-582
  • Peer Reviewed
• [Journal Article] Monoallelic BUB1B Mutations and Defective Mitotic-Spindle Checkpoint in Seven Families With Premature Chromatid Separation (PCS) Syndrome. (2006)
  • Author(s): S. Matsuura, Y. Matsumoto, K. Morishima, H. Izumi, H. Matsumoto, E. Ito, K. Tsutsui, J. Kobayashi, H. Tauchi, Y. Kajiwara, S. Hama, K. Kurisu, H. Tahara, M. Oshimura, K. Komatsu, Tatsuro Ikeuchi, Tadashi Kajii.
  • Journal Title: Amer J Med Genet. 140(4) Pages: 358-67
  • Peer Reviewed
• [Journal Article] Accumulation of Werner protein at DNA double-strand breaks in human cells (2005)
  • Author(s): Li Lan, Satoshi Nakajima, Kenshi Komatsu, Andre Nussenzweig, Akira Shimamoto, Junko Oshima, Akira Yasui
  • Journal Title: J Cell Sci. 118 Pages: 4153-4162
  • Peer Reviewed
• [Journal Article] Fanconi Anemia protein FANCD2 promotes Thompson LH and Takata M. immunoglobulin gene conversion and DNA repair through a mechanism related to homologous recombination. (2005)
  • Author(s): Yamamoto K, Hirano S, Ishiai M, Morishima K, Kitao H, Kimura M, Namikoshi K, Matsushita N, Arakawa H, Buerstedde JM, Komatsu K, Thompson LH, Takata M.
  • Journal Title: Mol. Cell. Biol. 25 Pages: 34-43
  • Peer Reviewed
• [Journal Article] Werner syndrome protein associates with gamma H2AX in a manner that depends upon NBS1 (2005)
  • Author(s): Cheng W, Kobbe G, Opresko P L, Arthur L M, Komatsu K, Sidman M M, Carney J P, Bohr V A.
  • Journal Title: FEBS Letters 579(6) Pages: 1350-1356
  • Peer Reviewed
• [Journal Article] Ataxia-telangiectasia-mutated dependent phosphorylation of Artemis in response to DNA damage (2005)
  • Author(s): Chen L, Morio T, Minegishi Y, Nakada S, Nagasawa M, Komatsu K, Chessa L, Villa A, Lecis D, Delia D, Mizutani S.
  • Journal Title: Cancer Science 96 Pages: 134-141
  • Peer Reviewed
• [Presentation] UV sensitivities of cells from Nijmegen breakage syndrome and the UV sensitivities of cells underlying gene (2007)
  • Author(s): K. Komatsu
  • Organizer: The 3rd Japan-US DNA Repair Meeting
  • Place of Presentation: Sendai
  • Year and Date: 20070500
• [Presentation] NBS1 foci formation and divergent roles in response to DNA NBS1 foci formation and damage-eliciting agents (2006)
  • Author(s): K. Komatsu
  • Organizer: The 2006 International Workshop on Ataxia-telangiectsia
  • Place of Presentation: Canada Banff
  • Year and Date: 20060900
• [Presentation] Human NBS1 functions in the repair of I-SCe-I-induced DSBs via Human NBS1 functions in the homologous recombination and independently of ATM (2005)
  • Author(s): K. Komatsu
  • Organizer: The 2005 International Workshop on Ataxia-telangiectsia
  • Place of Presentation: Italy Milan
  • Year and Date: 20050600
• [Book] Multiple roles of NBS1 for genotoxic and non-genotoxic stresses、Radiation Health Risk Science. (2009)
  • Author(s): Komatsu K, Nakamura K, Yanagihara Hi, Kobayashi. Shimada M, Tsuchida K
  • Total Pages: 183-192
  • Publisher: Springer
• [Book] NBS1 and MRE11 associate for regulation of checkpoints and for homologous recombination repair. International Congress Series 1299 (2007)
  • Author(s): K. Komatsu, A. Antoccia, S. Sakamoto, J. Kobayashi, S. Matsuura, H. Tauchi. Human
  • Total Pages: 158-163
  • Publisher: ELSEVIER
• [Remarks]
  • URL: http://www.rbc.kyoto-u.ac.jp/Genome/index.html
• [Patent(Industrial Property Rights)] DNA鎖間架橋の測定方法およびDNA鎖間架橋の修復速度の測定方法 (2007)
  • Inventor(s): 槌田謙、小松賢志
  • Industrial Property Rights Holder: 国立大学法人京都大学
  • Industrial Property Number: 特願・2005-207121
  • Filing Date: 2007-02-02
  • Acquisition Date: 2007-02-02
• [Patent(Industrial Property Rights)] DNA鎖間架橋の測定方法およびDNA鎖間架橋の修復速度の測定方法 (2005)
  • Inventor(s): 槌田謙、小松賢志
  • Industrial Property Rights Holder: 国立大学法人京都大学
  • Industrial Property Number: 特願・2005-207121
  • Filing Date: 2005-07-15
  • Acquisition Date: 2005-07-15