ゲノム修復における動的クロマチン構造変換

• Project Area: Dynamic chromatin structure and function
• Project/Area Number: 26116514
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Hiroshima University
• Principal Investigator: 田代 聡 広島大学, 原爆放射線医科学研究所, 教授 (20243610)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000); Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
• Keywords: 細胞核高次構造 / 相同組換え修復 / RAD51 / クロマチンドメイン

Outline of Annual Research Achievements

本研究では、分子細胞生物学的手法を用いてRAD51が集積する束状核内領域がHR factoryである可能性を検証する。ついで、HR factoryの構築メカニズムを解明するために、束状領域に集積しないRAD51変異体を用いたクロマチン構造関連因子を中心としたインタラクトーム解析を行う。これらの研究を通して、ゲノム修復における動的クロマチン構造の生物学的意義の解明に取り組む。平成26年度は、RAD51集積束状領域とRAD51タンパク質の動態解析を行い、ゲノム損傷が誘導された束状領域にはより多くのRAD51が集積してくることが明らかになった。さらに、束状領域と相同組換え修復のために形成された単鎖DNAとの局在関連解析を行い、ゲノム損傷誘導後に単鎖DNAがRAD51集積束状領域に形成されていることが確認され、束状領域で相同組換え修復が行われている可能性が示唆された。これらの知見を検証するために、平成27年度は超解像顕微鏡を用いたクロマチンドメイン、HR関連タンパク質と束状領域との局在関連解析を行い、相同組換え修復に関連するRPAなどのタンパク質が、RAD51集積束状領域に集積していることを確認した。興味深いことに、これらのタンパク質の集積は、クロマチンドメインの表面、あるいはクロマチン間領域に認められ、ゲノム修復の「場」と細胞核高次構造の関連の一端が明らかになった。

Research Progress Status

27年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

27年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] ミュンヘン大学(ドイツ)
• [Journal Article] Cytogenetic effects of radioiodine therapy: a 20-year follow-up study (2016)
  • Author(s): Livingston GK, Khvostunov IK, Gregoire E, Barquinero JF, Shi L, Tashiro S.
  • Journal Title: Radiate Environ Biophys. Volume: 55 Issue: 2 Pages: 201-213
  • DOI: 10.1007/s00411-016-0647-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Enhanced gefitinib-induced repression of the epidermal growth factor receptor pathway by ataxia telangiectasia-mutated kinase inhibition in non-small-cell lung cancer cells. (2016)
  • Author(s): Misumi K, Sun J, Kinomura A, Miyata Y, Okada M, Tashiro S.
  • Journal Title: Cancer Sci. Volume: 107 Issue: 4 Pages: 444-451
  • DOI: 10.1111/cas.12899
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Relaxed Chromatin Formation and Weak Suppression of Homologous Pairing by the Testis-Specific Linker Histone H1T. (2016)
  • Author(s): Machida S, Hayashida R, Takaku M, Fukuto A, Sun J, Kinomura A, Tashiro S, Kurumizaka H.
  • Journal Title: Biochemistry. Volume: 55 Issue: 4 Pages: 637-646
  • DOI: 10.1021/acs.biochem.5b01126
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Common Variant Near HEY2 Has a Protective Effect on Ventricular Fibrillation Occurrence in Brugada Syndrome by Regulating the Repolarization Current. (2016)
  • Author(s): Nakano Y, Ochi H, Onohara Y, Toshishige M, Tokuyama T, Matsumura H, Kawazoe H, Tomomori S, Sairaku A, Watanabe Y, Ikenaga H, Motoda C, Suenari K, Hayashida Y, Miki D, Oda N, Kishimoto S, Oda N, Yoshida Y, Tashiro S, Chayama K, Kihara Y.
  • Journal Title: Circ Arrhythm Electrophysiol. Volume: 9(1) Issue: 1
  • DOI: 10.1161/circep.115.003436
  • Peer Reviewed
• [Journal Article] hCAS/CSE1L regulates RAD51 distribution and focus formation for homologous recombinational repair (2015)
  • Author(s): 1.Okimoto S, Sun J, Fukuto A, Horikoshi Y, Matsuda S, Matsuda T, Ikura M, Ikura T, Machida S, Kurumizaka H, Miyamoto Y, Oka M, Yoneda Y, Kiuchi Y, Tashiro S.
  • Journal Title: Genes Cells. Volume: 20 Issue: 9 Pages: 681-94
  • DOI: 10.1111/gtc.12262
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Regulation of homologous recombinational repair by lamin B1 in radiation-induced DNA damage.ional repair by lamin B1 in radiation-induced DNA damage. (2015)
  • Author(s): Liu NA, Sun J, Kono K, Horikoshi Y, Ikura T, Tong X, Haraguchi T, Tashiro S.
  • Journal Title: FASEB J Volume: 29 Pages: 2514-2525
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Regulation of homologous recombinational repair by lamin B1 in radiation-induced DNA damage. (2015)
  • Author(s): Liu NA
  • Journal Title: FASEB J Volume: 29 Pages: 1-13
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Nap1 stimulates homologous recombination by RAD51 and RAD54 in higher-ordered chromatin containing histone H1. (2014)
  • Author(s): Machida, S., Takaku, M., Ikura, M., Sun, J., Suzuki, H., Kobayashi, W., Kinomura, A., Osakabe, A., Tachiwana, H., Horikoshi, Y., Fukuto, A., Matsuda, R., Ura, K., Tashiro, S., Ikura, T., and Kurumizaka, H.
  • Journal Title: Scientific Rep. Volume: 4 Issue: 1 Pages: 4863-4863
  • DOI: 10.1038/srep04863
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Reorganization of Damaged Chromatin by the Exchange of Histone Variant H2A.Z-2. (2014)
  • Author(s): Nishibuchi I
  • Journal Title: Int J Radiat Oncol Biol Phys. Volume: 89 Issue: 4 Pages: 736-744
  • DOI: 10.1016/j.ijrobp.2014.03.031
  • Peer Reviewed / Open Access
• [Journal Article] Smoking cessation reverses DNA double-strand breaks in human mononuclear cells. (2014)
  • Author(s): Ishida M
  • Journal Title: PLoS One Volume: 9 Issue: 8 Pages: 1-9
  • DOI: 10.1371/journal.pone.0103993
  • Peer Reviewed / Open Access
• [Journal Article] The transcription repressors Bach2 and Bach1 promote B cell development by repressing myeloid program. (2014)
  • Author(s): Itoh-Nakadai A, Hikota R, Muto A, Kometani K, Matsui-Watanabe M, Sato Y, Kobayashi M, Nakamura A, Miura Y, Yano Y, Tashiro S, Sun J, Ikawa T, Ochiai K, Kurosaki T, and Igarashi K.
  • Journal Title: Nature Immunol. Volume: 15 Issue: 12 Pages: 1171-1180
  • DOI: 10.1038/ni.3024
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] CT scan-induced DNA damage in children measured using molecular markers and nanoscope technology, (2016)
  • Author(s): Tashiro S.
  • Organizer: 14th International Workshop on Radiation Damage to DNA
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2016-03-22
  • Int'l Joint Research / Invited
• [Presentation] 放射線誘発核内ドメインの構造構築 (2015)
  • Author(s): 田代 聡
  • Organizer: 第38回 日本分子生物学会年会・ 第88回 日本生化学会大会 合同大会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-12-04
• [Presentation] Regulation of DNA repair and Nuclear Lamina (2015)
  • Author(s): Tashiro S.
  • Organizer: International Symposium on Chromatin Structure, Dynamics, and Function
  • Place of Presentation: 淡路市
  • Year and Date: 2015-08-25
  • Int'l Joint Research
• [Presentation] Nuclear Topography of homologous recombinational repair (2015)
  • Author(s): Tashiro S.
  • Organizer: 15th International Congress of Radiation Research (ICRR 2015)
  • Place of Presentation: 京都市
  • Year and Date: 2015-05-28
  • Int'l Joint Research / Invited
• [Presentation] Biological Estimation of the DNA Damage Induced by CT Scan. (2015)
  • Author(s): Tashiro S.
  • Organizer: 15th International Congress of Radiation Research (ICRR 2015)
  • Place of Presentation: 京都市
  • Year and Date: 2015-05-27
  • Int'l Joint Research / Invited
• [Presentation] 放射線によるゲノム損傷と修復 (2014)
  • Author(s): 田代 聡
  • Organizer: 広島医学会総会シンポジウム
  • Place of Presentation: 広島市
  • Year and Date: 2014-11-09
• [Presentation] 染色体ストレス応答の再構成と複合システムとしての理解 (2014)
  • Author(s): 田代 聡
  • Organizer: 第87回 日本生化学会大会シンポジウム
  • Place of Presentation: 京都市
  • Year and Date: 2014-10-15
• [Presentation] 医療放射線被ばくによるゲノム損傷評価法の確立 (2014)
  • Author(s): 田代 聡
  • Organizer: 日本放射線影響学会 第57回大会 シンポジウム
  • Place of Presentation: 鹿児島市
  • Year and Date: 2014-10-03
• [Presentation] 相同組換え修復における損傷クロマチン動態 (2014)
  • Author(s): 田代 聡
  • Organizer: 第52回 日本生物物理学会年会
  • Place of Presentation: 札幌市
  • Year and Date: 2014-09-26
  • Invited
• [Presentation] Nuclear topography of homologous recombinational repair (2014)
  • Author(s): Tashiro S
  • Organizer: Cold Spring Harbor meeting
  • Place of Presentation: ニューヨーク（アメリカ）
  • Year and Date: 2014-08-23 – 2014-08-26
• [Remarks] 細胞修復制御研究分野 原爆放射線医科学研究所 広島大学
  • URL: http://home.hiroshima-u.ac.jp/cellbio/