Functional analysis of CUL4/DDB1 ubiquitin E3 ligase in DNA damage response

• Project/Area Number: 21510055
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Kanazawa University
• Principal Investigator: WAKASUGI Mitsuo 金沢大学, 薬学系, 助教 (80345595)
• Co-Investigator(Kenkyū-buntansha): MATSUNAGA Tsukasa 金沢大学, 薬学系, 教授 (60192340)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: ゲノム / シグナル伝達 / DNA損傷応答 / ユビキチン / DNA修復 / クロマチン

Research Abstract

The Cul4/DDB1 complex is a recently identified culling-RING ubiquitin ligase, which regulates DNA repair, DNA replication and transcription. We analyzed the potential functions of DDB1 in the responses to various DNA damaging agents using a conditional knockout DT40 cells. Furthermore, we found that the interaction between DDB1 and Cul4 is absolutely required for cell viability, suggesting an essential role of DDB1 as a component of Cul4/DDB1 ubiquitin E3 ligase.

Research Products

• [Journal Article] SCF β TrCP mediates stress-activated MAP kinase-induced Cdc25B degradation. (2014)
  • Author(s): Uchida, S, et al.
  • Journal Title: J Cell Sci. Volume: 124 Issue: 16 Pages: 2816-2825
  • DOI: 10.1242/jcs.083931
  • Peer Reviewed
• [Journal Article] Establishment of a microplate for mattedcell-based immunoassay for rapid analysis of nucleotide excision repair ability in human primary cells (2012)
  • Author(s): Nishinaga M, Kurata R, Onishi K, Kuriyama K, Wakasugi M, Matsunaga T.
  • Journal Title: Photochem. Photobiol Volume: 88 Issue: 2 Pages: 356-62
  • DOI: 10.1111/j.1751-1097.2012.01073.x
  • Peer Reviewed
• [Journal Article] The molecular basis of CRL4DDB2/CSA ubiquitin ligase architecture, targeting, and activation (2011)
  • Author(s): Fischer, E.S., et al
  • Journal Title: Cell Volume: 147 Issue: 5 Pages: 1024-1039
  • DOI: 10.1016/j.cell.2011.10.035
  • Peer Reviewed
• [Journal Article] 休止期におけるヌクレオチド除去修復依存的な二次的DNA損傷の生成 (2011)
  • Author(s): 若杉光生, 松永司
  • Journal Title: 放射線生物研究 Volume: 46 Pages: 322-331
  • URL: http://www.naramed-u.ac.jp/~oncra/rbrc/
• [Journal Article] Role of interaction of XPF with RPA in nucleotide excision repair (2011)
  • Author(s): Fisher LA, Bessho M, Wakasugi M, Matsunaga T, Bessho T.
  • Journal Title: J Mol Biol Volume: 413 Issue: 2 Pages: 337-346
  • DOI: 10.1016/j.jmb.2011.08.034
  • Peer Reviewed
• [Journal Article] Optimized gene silencing by co-expression of multiple shRNAs in a single vector. (2010)
  • Author(s): Ishigaki, Y.
  • Journal Title: Methods Mol.Biol. Volume: 623 Pages: 109-121
• [Journal Article] Physical and functional interaction between DDB and XPA innucleotide excision repair (2009)
  • Author(s): Wakasugi M, Kasashima H, Fukase Y, Imura M, Imai R, Yamada S, Cleaver JE, Matsunaga T.
  • Journal Title: Nucleic Acids Res Volume: 37 Issue: 2 Pages: 516-525
  • DOI: 10.1093/nar/gkn964
  • Peer Reviewed
• [Journal Article] Stress-activated mitogen-activated protein kinases c-Jun NH2-terminal kinase and p38 target Cdc25B for degradation (2009)
  • Author(s): Uchida S, Yoshioka K, Kizu R, Nakagama H, Matsunaga T, Ishizaka Y, Poon RY, Yamashita K.
  • Journal Title: Cancer Res Volume: 69 Pages: 6438-44
  • NAID: 120001613724
  • Peer Reviewed
• [Journal Article] Physical and functional interaction between DDB and XPA in nucleotide excision repair (2009)
  • Author(s): Wakasugi, M
  • Journal Title: Nucleic Acids Research 37 Pages: 516-525
  • Peer Reviewed
• [Journal Article] Stress-activated MAP kinases JNK and p38 target Cdc25B for degradation (2009)
  • Author(s): Uchida, S
  • Journal Title: Cancer Research 69 Pages: 6438-6444
  • Peer Reviewed
• [Presentation] ヌクレオチド除去修復能の新規解析系の開発とその応用 (2012)
  • Author(s): 松永司
  • Organizer: 国立遺伝学研究所研究集会
  • Place of Presentation: 国立遺伝学研究所(静岡県)
  • Year and Date: 2012-02-10
• [Presentation] ヌクレオチド除去修復能の新規解析系の開発とその応用 (2012)
  • Author(s): 松永司
  • Organizer: 国立遺伝学研究所研究集会「ユビキチン・SUMOによるDNA複製およびBNA修復系の制御」
  • Place of Presentation: 国立遺伝学研究所(静岡県)(招待講演)
  • Year and Date: 2012-02-10
• [Presentation] 休止期のヌクレオチド除去修復に伴う二重鎖切断の生成とATMシグナリング経路の活性化 (2011)
  • Author(s): 若杉光生
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2011-12-15
• [Presentation] 休止期細胞におけるヌクレオチド除去修復に依存した二重鎖切断の生成とATMシグナリング経路の活性化 (2011)
  • Author(s): 若杉光生
  • Organizer: 日本放射線影響学会第54回大会
  • Place of Presentation: 神戸商工会議所会館(兵庫県)
  • Year and Date: 2011-11-18
• [Presentation] Application of a cell-based immunoassay for nucleotlde excision repair (2011)
  • Author(s): Nishinaga M
  • Organizer: The 5th Asia and Oceania Conference on Photobiology
  • Place of Presentation: Nara Prefectural New Public Hall(奈良県)
  • Year and Date: 2011-07-31
• [Presentation] ヒトG0期細胞におけるヌクレオチド除去修復に伴うATRとATMの活性化 (2010)
  • Author(s): 松永司
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会
  • Place of Presentation: 神戸国際展示場(兵庫県)
  • Year and Date: 2010-12-09
• [Presentation] ヒトGO期細胞におけるヌクレオチド除去修復に伴うATRとATMの活性化 (2010)
  • Author(s): 松永司
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会
  • Place of Presentation: 神戸国際展示場(兵庫県)
  • Year and Date: 2010-12-09
• [Presentation] ユビキチンE3リガーゼコンポーネントとしてのDDB1の機能解析 (2010)
  • Author(s): 若杉光生
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会
  • Place of Presentation: 神戸国際展示場(兵庫県)
  • Year and Date: 2010-12-08
• [Presentation] 紫外線照射後のピストンH2AX修飾反応の解析 (2010)
  • Author(s): 金山昌代
  • Organizer: 日本薬学会北陸支部第122回例会
  • Place of Presentation: 北陸大学(石川県)
  • Year and Date: 2010-11-21
• [Presentation] Essential role of DDB1 as a component of DDB1-CUL4 ubiquitin E3 ligase (2010)
  • Author(s): Kawaguchi, Y.
  • Organizer: 7th 3R(Replica-tion, Recombination and Repair) Symposium
  • Place of Presentation: Toyama international conference center(Toyama)
  • Year and Date: 2010-10-29
• [Presentation] Analysis of DNA repair activity in various human cells using a cell-based immunoassay (2010)
  • Author(s): Nishinaga, M.
  • Organizer: 7th 3R (Replication, Recombination and Repair) Symposium
  • Place of Presentation: 富山国際会議場(富山県)
  • Year and Date: 2010-10-29
• [Presentation] Essential role of DDB1 as a component of DDBI-CDL4 ubiquitin E3 ligase (2010)
  • Author(s): Kawaguchi, Y.
  • Organizer: 7th 3R (Replication, Recombination and Repair) Symposium
  • Place of Presentation: 富山国際会議場(富山県)
  • Year and Date: 2010-10-27
• [Presentation] 紫外線照射されたG0期細胞におけるヌクレオチド除去修復に依存した二次的DNA損傷の生成 (2010)
  • Author(s): 若杉光生
  • Organizer: 日本放射線影響学会第53回大会
  • Place of Presentation: 京都テルサ(京都府)
  • Year and Date: 2010-10-21
• [Presentation] 紫外線照射されたGO期細胞におけるヌクレオチド除去修復に依存した二次的DNA損傷の生成 (2010)
  • Author(s): 若杉光生
  • Organizer: 日本放射線影響学会第53回大会
  • Place of Presentation: 京都テルサ(京都府)
  • Year and Date: 2010-10-21
• [Presentation] DDB1-Cul4 E3リガーゼの機能解析 (2010)
  • Author(s): 松永司
  • Organizer: 国立遺伝学研究所研究集会
  • Place of Presentation: 国立遺伝学研究所(静岡県)
  • Year and Date: 2010-10-01
• [Presentation] DDB1-Cul4 E3リガーゼの機能解析 (2010)
  • Author(s): 松永司
  • Organizer: 国立遺伝学研究所研究集会
  • Place of Presentation: 国立遺伝学研究所(静岡県)(招待講演)
  • Year and Date: 2010-10-01
• [Presentation] 末梢血由来リンパ球を用いたヌクレオチド除去修復能診断系の開発 (2010)
  • Author(s): 松永司
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪府)
  • Year and Date: 2010-09-24
• [Presentation] 末梢血リンパ球を用いたヌクレオチド除去修復能診断法の開発と発がんリスク評価への応用 (2010)
  • Author(s): 松永司
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪府)
  • Year and Date: 2010-09-24
• [Presentation] DNA損傷によるChk1キナーゼの活性化とその制御 (2010)
  • Author(s): 松永司
  • Organizer: 平成22年度専門研究会
  • Place of Presentation: 京都大学原子炉実験所(大阪府)
  • Year and Date: 2010-09-11
• [Presentation] DNA損傷によるChk1キナーゼの活性化とその制御 (2010)
  • Author(s): 松永司
  • Organizer: 平成22年度専門研究会
  • Place of Presentation: 京都大学原子炉実験所(大阪府)(招待講演)
  • Year and Date: 2010-09-11
• [Presentation] 末梢血由来リンパ球を用いたヌクレオチド除去修復能診断系の開発 (2010)
  • Author(s): 西山千晶
  • Organizer: 第32回 日本光医学光生物学会
  • Place of Presentation: 東京慈恵会医科大学(東京都)
  • Year and Date: 2010-07-31
• [Presentation] Modulation ofnucleotide excision repair in human cells (2010)
  • Author(s): Wakasugi, M.
  • Organizer: International Confernece on Radiation and Cancer Biology at Nagasaki 2010
  • Place of Presentation: Matsumoto Ryojun Auditorium Bawdwin Hall(Nagasaki)
  • Year and Date: 2010-02-18
• [Presentation] Modulation of nucleotide excision repair in human cells (2010)
  • Author(s): Wakasugi, M
  • Organizer: International Confernece on Radiation and Cancer Biology at Nagasaki 2010
  • Place of Presentation: Matsumoto Ryojun Auditorium Bawdwin Hall (Nagasaki)
  • Year and Date: 2010-02-18
• [Presentation] EdUを用いたマウスT細胞刺激後分裂動態の細胞周期による評価 (2009)
  • Author(s): 安藤由顕
  • Organizer: 日本薬学会北陸支部第121回例会
  • Place of Presentation: 富山大学杉谷キャンパス (富山県)
  • Year and Date: 2009-12-06
• [Presentation] Histone H2AX phosphorylation triggered by nucleotide excision repair intermediates in quiescent cells (2009)
  • Author(s): Matsunaga, T.
  • Organizer: Keystone Symposia "Telomere Biology and DNA Repair"
  • Place of Presentation: RACV Royal Pines Resort(Australia)
  • Year and Date: 2009-10-11
• [Presentation] The role of caspase-Dependent Chk1 cleavage during apoptosis (2009)
  • Author(s): Matuura, K.
  • Organizer: Telomere Biology and DNA Repair
  • Place of Presentation: RACV Royal Pines Resort(Australia)
  • Year and Date: 2009-10-11
• [Presentation] Histone H2AX phosphorylation triggered by nucleotide excision repair intermediates-in quiescent cells (2009)
  • Author(s): 松永司
  • Organizer: Keystone Symposia "Telomere Biology and DNA Repair"
  • Place of Presentation: RACV Royal Pines Resort (Australia)
  • Year and Date: 2009-10-11
• [Presentation] The role of caspase-dependent Chk1 cleavage during apoptosis (2009)
  • Author(s): Matsuura, K
  • Organizer: Keystone Symposia "Telomere Biology and DNA Repair"
  • Place of Presentation: RACV Royal Pines Resort (Australia)
  • Year and Date: 2009-10-11
• [Presentation] 癌細胞におけるDNA損傷/複製ストレス後のChk1リン酸化の異常亢進 (2009)
  • Author(s): 松永司
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2009-10-01
• [Presentation] 癌細胞におけるDNA損傷/複製ストレス後のChk1リン酸化の異常亢進 (2009)
  • Author(s): 松永司
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜 (神奈川県)
  • Year and Date: 2009-10-01
• [Presentation] Cell-based assay を用いた紫外線誘発DNA損傷検出系の開発 (2009)
  • Author(s): 西永真理
  • Organizer: 第31年日本光医学光生物学会
  • Place of Presentation: 梅田スカイビル (大阪府)
  • Year and Date: 2009-07-25
• [Presentation] 紫外線誘発DNA損傷に対するヌクレオチド除去修復能を評価する簡易診断システムの開発 (2009)
  • Author(s): 西山千晶
  • Organizer: 第31年日本光医学光生物学会
  • Place of Presentation: 梅田スカイビル (大阪府)
  • Year and Date: 2009-07-25
• [Remarks]
  • URL: http://www.p.kanazawa-u.ac.jp/~iden/
• [Remarks]
  • URL: http://www.p.kanazawa-u.ac.jp/~iden/
• [Remarks]
  • URL: http://www.p.kanazawa-u.ac.jp/~iden/gyoseki/index.html
• [Remarks]
  • URL: http://www.p.kanazawa-u.ac.jp/~iden/gyoseki/index.html
• [Patent(Industrial Property Rights)] DNA損傷修復能力の簡便・迅速な検査方法 (2010)
  • Inventor(s): 松永司、西山千晶
  • Industrial Property Rights Holder: 金沢大学
  • Industrial Property Number: 2010-155303
  • Filing Date: 2010-07-07
• [Patent(Industrial Property Rights)] DNA損傷修復能力の簡便・迅速な検査方法 (2010)
  • Inventor(s): 松永司, 西山千晶
  • Industrial Property Rights Holder: 金沢大学
  • Industrial Property Number: 2010-155303
  • Filing Date: 2010-07-07