Roles of newly discovered NBS1 domains in ubiquitin signals and rejoining of double-strand breaks after irradiation

• Project/Area Number: 23241021
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Kyoto University
• Principal Investigator: KOMATSU Kenshi 京都大学, 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, 准教授 (30301302) ; KATO Akihiro 京都大学, 放射線生物研究センター, 研究員 (70423051)
• Project Period (FY): 2011-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥37,700,000 (Direct Cost: ¥29,000,000、Indirect Cost: ¥8,700,000); Fiscal Year 2013: ¥12,480,000 (Direct Cost: ¥9,600,000、Indirect Cost: ¥2,880,000); Fiscal Year 2012: ¥12,480,000 (Direct Cost: ¥9,600,000、Indirect Cost: ¥2,880,000); Fiscal Year 2011: ¥12,740,000 (Direct Cost: ¥9,800,000、Indirect Cost: ¥2,940,000)
• Keywords: 損傷乗越えDNA合成 / NBS1 / 損傷乗り越えDNA合成 / クロマチン・リモデリング / RNF20 / RAD18 / ATM / FACT / 相同組み換え修復 / 非相同末端再結合 / レポーター遺伝子

Outline of Final Research Achievements

NBS1, a protein responsible for radiation sensitive disorder, has been to control both cell cycle checkpoint and homologous recombination repair by binding to either ATM or MRE11 at the C-terminus of NBS1. We hosed here other two binding regions at the C-terminus and their regulatory mechanisms. NBS1 ubiquitinates PCNA and then initiates Pol eta-mediated translesional DNA synthesis by binding to RAD18. It also binding to RNF20 to ubiquitinate histone H2B, which,in turn, recruits histone chaperon FACT and initiates chromatin-remodeling for rejoining of DNA double-strand break.

Research Products

• [Journal Article] Histone chaperone FACT regulates homologous recombination by chromatin remodeling through interaction with RNF20. (2014)
  • Author(s): Oliveira DV, Kato A, Nakamura K, Ikura T, Okada M, Kobayashi J, Yanagihara H, Saito Y, Tauchi H, Komatsu K
  • Journal Title: J Cell Sci Volume: 127 Pages: 763-772
  • DOI: 10.1242/jcs.135855
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] ATM regulates Cdt1 stability during the unperturbed S phase to prevent re-replication. (2014)
  • Author(s): Iwahori S, Kohmon D, Kobayashi J, Tani Y, Yugawa T, Komatsu K, Kiyono T, Sugimoto N, Fujita M.
  • Journal Title: Cell Cycle Volume: 13 Issue: 3 Pages: 471-481
  • DOI: 10.4161/cc.27274
  • Peer Reviewed / Open Access
• [Journal Article] Mutations in the FHA-domain of ectopically expressed NBS1 lead to Radiosensitization and to no increase in somatic mutation rates via a partial suppression of homologous recombination (2014)
  • Author(s): Maki Ohara, Yumi Funyu, Shunsuke Ebara, Yuki Sakamoto, Ryota Seki, Kenta Iijima, Akiko Ohishi, Junya Kobayashi, Kenshi Komatsu, Akira Tachibana, and Hiroshi Tauchi
  • Journal Title: J. Radiat. Res Volume: 55 Issue: 4 Pages: 690-698
  • DOI: 10.1093/jrr/rru011
  • Peer Reviewed / Open Access
• [Journal Article] Hypergonadotropic Hypogonadism and Hypersegmented Neutrophils in a Patient with Ataxia-Telangiectasia-Like Disorder: Potential Diagnostic Clues? (2014)
  • Author(s): Yoshida T, Awaya T, Shibata M, Kato T, Numabe H, Kobayashi K, Komatsu K, Heike T
  • Journal Title: Am J Med Genet A Volume: 164
  • NAID: 120005456013
  • Peer Reviewed
• [Journal Article] The proteasome factor Bag101 binds to Rad22 and suppresses homologous recombination. (2013)
  • Author(s): Saito Y, Takeda J, Okada M, Kobayashi J, Kato A, Hirota K, Taoka M, Matsumoto T, Komatsu K, Isobe T.
  • Journal Title: Sci Rep. Volume: 3 Issue: 1 Pages: 2022-2022
  • DOI: 10.1038/srep02022
  • Peer Reviewed
• [Journal Article] High LET radiation amplifies centrosome overduplication through a pathway of γ-tubulin monoubiquitination (2013)
  • Author(s): Shimada M, Hirayama R, Komatsu K.
  • Journal Title: International Journal of Radiation Oncology,Biology,Physics Volume: 86 Issue: 2 Pages: 358-365
  • DOI: 10.1016/j.ijrobp.2013.01.010
  • NAID: 120005245135
  • Peer Reviewed
• [Journal Article] DNA damage sensor MRE11 recognizes cytosolic double-stranded DNA and induces type I interferon by regulating STING traffickining (2013)
  • Author(s): Takeshi Kondo, Junya Kobayashi, Tatusya Saitoh, Kenta Maruyama. Ken J. Ishii, Glen N. Barber, Kenshi、Komatsu, Shizuo Akira, and Taro Kawai
  • Journal Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 110 Issue: 8 Pages: 2969-2974
  • DOI: 10.1073/pnas.1222694110
  • Peer Reviewed
• [Journal Article] DNA-PK inhibition causes a low level of H2AX phosphorylation and homologous recombination repair in Medaka (Oryzias latipes) cells. Biochem. (2012)
  • Author(s): Urushihara, Y., Kobayashi, J., Matsumoto, Y., Komatsu, K, Oda, S., Mitani, H.
  • Journal Title: Biophys.Res.Commun. Volume: 429 Issue: 3-4 Pages: 131-136
  • DOI: 10.1016/j.bbrc.2012.10.128
  • Peer Reviewed
• [Journal Article] Generation and characterization of severe combined immune deficientrats. (2012)
  • Author(s): Mashimo T, Takizawa A, Kobayashi J, Kunihiro Y, Yoshimi K, Ishida S, Tanabe K, Yanagi A, Tachibana A, Hirose J, Yomoda J, Morimoto S, Kuramoto T, Voigt B, Watanabe T, Hiai H, Tateno C, Komatsu K, Serikawa T.
  • Journal Title: Cell Reports Volume: 2(3) Issue: 3 Pages: 685-694
  • DOI: 10.1016/j.celrep.2012.08.009
  • Peer Reviewed
• [Journal Article] NBS1 recruits RAD18 via aRAD6-like domain and regulates Polη-dependent translesion DNA synthesis (2011)
  • Author(s): Yanagihara H, Kobayashi J, Tateishi S, Kato A, Matsuura S, Tauchi H, Yamada K, Takezawa J, Sugasawa K, Masutani C, Hanaoka F, Weemaes CM, Mori T, Zou L, Komatsu K.
  • Journal Title: Mol Cell Volume: 43 Issue: 5 Pages: 788-797
  • DOI: 10.1016/j.molcel.2011.07.026
  • Peer Reviewed
• [Journal Article] Genistein, isoflavonoids in soybeans, prevents the formation of excess radiation-induced centrosomes via p21up-regulation (2011)
  • Author(s): Shimada M, Kato A, Habu T, Komatsu K
  • Journal Title: Mutatation Research Volume: Volume 716 Issue: 1-2 Pages: 27-32
  • DOI: 10.1016/j.mrfmmm.2011.07.017
  • Peer Reviewed
• [Journal Article] Possible role of WRN protein in cellular response induced by a little DNA damage (2011)
  • Author(s): Kobayashi, J.
  • Journal Title: Fusion Sicence and Technology Volume: 60 Pages: 1186-1189
  • Peer Reviewed
• [Presentation] NBS1 plays a role in UV damage response through physical interaction with RAD18 (2014)
  • Author(s): A Kato, H Yanagihara, J Kobayashi, Y Saito, D Oliveira, C Weemaes, and K Komatsu.
  • Organizer: International Symposium on Xeroderma Pigmentosum and Related Diseases
  • Place of Presentation: Kobe
  • Invited
• [Presentation] NBS1による損傷乗り越えDNA合成開始機構とモデルマウスの開発 (2013)
  • Author(s): 柳原啓見、加藤晃弘、小林純也、斎藤裕一朗、前川貴則、谷崎美智、小松賢志
  • Organizer: 日本放射線影響学会第56回大会
  • Place of Presentation: 青森
• [Presentation] A Kato, H Yanagihara, K Komatsu. Distinct domains of NBS1 separately function in IR- and UV-damage response. (2013)
  • Author(s): A Kato, H Yanagihara, K Komatsu
  • Organizer: The DNA damage response in cell physiology and disease
  • Place of Presentation: Cape Sounio
• [Presentation] 紫外線と放射線のDNA修復に共通した開始機構 (2013)
  • Author(s): 小松賢志
  • Organizer: 太陽紫外線防御研究会
  • Place of Presentation: 神戸
  • Invited
• [Presentation] Novel Role of NBS1 in Ubiquitination-Mediated Response through RNF20 (2012)
  • Author(s): Kobayashi, J.
  • Organizer: 14th International Workshop on Ataxia-Telangiectasia (ATW2012)
  • Place of Presentation: New Delhi (India)(招待講演)
  • Year and Date: 2012-02-11
• [Presentation] The roles of NBS1 in responses to radiation- and UV-induced DNA damage (2012)
  • Author(s): Komatsu、K.
  • Organizer: The Sugahara Memorial International Symposium
  • Place of Presentation: 京都大学(招待講演)
  • Year and Date: 2012-01-25
• [Presentation] DNA損傷修復研究の20年間 (2012)
  • Author(s): 小松賢志
  • Organizer: 日本放射線影響学会第55回大会
  • Place of Presentation: 仙台
  • Invited
• [Presentation] H2B ubiquitination-mediated chromatin remodeling in response to double-stranded DNA breaks in vertbrates (2011)
  • Author(s): Komatsu、K.
  • Organizer: 日本分子生物学会
  • Place of Presentation: パシフィコ横浜(招待講演)
  • Year and Date: 2011-12-15
• [Presentation] CONTROL OF HOMOLOGOUS RECOMBINATION BY RNF20-DEPENDENT H2B UBIQUITINATION (2011)
  • Author(s): Komatsu、K.
  • Organizer: 27th RBC-NIRS International Symposium
  • Place of Presentation: コープ.イン.京都(招待講演)
  • Year and Date: 2011-12-09
• [Presentation] NBS1を中心とした放射線損傷応答の最近の進歩 (2011)
  • Author(s): Komatsu、K.
  • Organizer: 第2回国際放射線神経生物学会
  • Place of Presentation: 群馬大学(招待講演)
  • Year and Date: 2011-12-03
• [Presentation] DNA二重鎖切断におけるクロマチン・リモデリング因子とその制御機構 (2011)
  • Author(s): Komatsu、K.
  • Organizer: 環境エピゲノミクス研究会第5回定例会
  • Place of Presentation: 大阪府立大学(招待講演)
  • Year and Date: 2011-05-14
• [Presentation] 若年期マウスのDNA修復能力と放射線感受性
  • Author(s): 小松賢志
  • Organizer: 環境研セミナー
  • Place of Presentation: 六カ所村
  • Invited
• [Book] 先天代謝異常症候群（第二版） (2012)
  • Author(s): 柳原啓見
  • Publisher: 日本臨床社
• [Book] DNA修復とゲノム不安定性 (2011)
  • Author(s): 小松賢志
  • Publisher: がん生物学イラストレイテッド、羊土社
• [Book] The Potential Role of DNA Repair Proteins in Centrosome Maintenance (2011)
  • Author(s): Shimada, M.
  • Publisher: DNA repair Intech publisher
• [Remarks]
  • URL: http://www.rbc.kyoto-u.ac.jp/index.htm