Molecular analysis of microhomology-mediated end-joining in DNA repair

• Project/Area Number: 19590311
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Kumamoto University
• Principal Investigator: KUWAHARA Kazuhiko Kumamoto University, 大学院・医学薬学研究部, 准教授 (10263469)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2007: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: DNA損傷 / 相同組換え / 非相同末端接合 / クラススイッチ / 微小相同組換え

Research Abstract

GANP分子のDNA組換え制御機構に関して、βガラクトシダーゼ遺伝子を用いた組換え検出系によりGANPの相同組換え抑制に関しては中央部分のSac3相同領域が重要であること、またこの組換え抑制は二重鎖切断後に起こることが明らかとなった。さらにGANP欠損B細胞を用いてクラススイッチの解析を行うとIL-4と抗CD40抗体の共刺激による誘導で微小相同組換えによる修復が増加していた。以上の結果よりGANPはDNA修復において相同組換え、微小相同組換えを制御する役割を持つことが示された。

Research Products

• [Journal Article] GANP suppresses the arginine methyltransferase PRMT5 regulating IL-4-mediated STAT6-signaling to IgE production in B cells (2009)
  • Author(s): Hideya Igarashi, Kazuhiko Kuwahara, Mikoto Yoshida, Yan Xing, Kazuhiko Maeda, Koichi Nakajima, & Nobuo Sakaguchi
  • Journal Title: Mol. Immunol 46 Pages: 1031-1041
  • Peer Reviewed
• [Journal Article] GANP suppresses the arginine methyltransferase PRMT5 regulating IL-4-mediated STAT6-signaling to IgE production in B cells. (2009)
  • Author(s): Igarashi H.
  • Journal Title: Molecular Immunology 46 Pages: 1031-1041
  • Peer Reviewed
• [Journal Article] Germinal center B-cell-associated DNA hypomethylation at transcriptional regions of the AID gene (2008)
  • Author(s): Satoru Fujimura, Takeshi Matsui, Kazuhiko Kuwahara, Kazuhiko Maeda, & Nobuo Sakaguchi
  • Journal Title: Mol. Immunol 45 Pages: 1712-1719
  • Peer Reviewed
• [Journal Article] Germinal center B-cell-associated DNA hypomethylation at transcriptional regions of the AID gene. (2008)
  • Author(s): Fujimura S.
  • Journal Title: Molecular Immunology 45 Pages: 1712-1719
  • Peer Reviewed
• [Journal Article] Germinal center B-cell-associated DNA hypomethylation at transcriptional regions of the AID gene. (2008)
  • Author(s): Fujimura S.
  • Journal Title: Molecular Immunology 45(6) Pages: 1712-1719
  • Peer Reviewed
• [Journal Article] GANP suppresses DNA recombination, measured by direct-repeat β-galactosidase gene construct, but does not suppress the type of recombination applying to immunoglobulin genes in mammalian cells (2007)
  • Author(s): Mikoto Yoshida, Kazuhiko Kuwahara, Tatsuya Shimasaki, Naomi Nakagata, Masao Matsuoka, & Nobuo Sakaguchi
  • Journal Title: Genes Cells 12 Pages: 1205-1213
  • Peer Reviewed
• [Journal Article] GANP suppresses DNA recombination, measured by direct-repeat β-galactosidase gene construct, but does not suppress the type of recombination applying to immunoglobulin genes inmammalian cells. (2007)
  • Author(s): Yoshida M.
  • Journal Title: Genes to Cells 12(10) Pages: 1205-1213
  • Peer Reviewed
• [Presentation] Functional differences between GANP and THP1 molecules in B cell activation and development (2008)
  • Author(s): Kazuhiko Kuwahara
  • Organizer: 第37回日本免疫学会学術集会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2008-12-01
• [Presentation] Functional differences between GANP and THP1 in B cell activation and development. (2008)
  • Author(s): Kuwahara K.
  • Organizer: 日本免疫学会学術集会
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2008-12-01
• [Presentation] Occurrence of sporadic breast cancer is associated with decrease of GANP causing abnormal sister chromatid cohesion (2008)
  • Author(s): Kazuhiko Kuwahara
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2008-10-28
• [Presentation] GANP分子発現低下による姉妹染色分体接着異常とその発癌における役割 (2008)
  • Author(s): 桑原一彦
  • Organizer: 第12回基盤的癌免疫研究会
  • Place of Presentation: 大宮ソニックシティー
  • Year and Date: 2008-07-02
• [Presentation] GANP分子発現低下による姉妹染色分体接着異常とその発癌における役割 (2008)
  • Author(s): 桑原一彦
  • Organizer: 第12回がん分子標的治療研究会
  • Place of Presentation: 総合学術センター
  • Year and Date: 2008-06-26
• [Presentation] Occurrence of sporadic breast cancer is significantly associated with the decreased expression of GANP, a mammalian homologue of Saccharomyces cerevisiae Sac3 (2008)
  • Author(s): Kazuhiko Kuwahara
  • Organizer: The Asia-Africa International Network Symposium of JSPS Asia and Africa Science Platform Program and The Fourth LiverCare Center Symposium
  • Place of Presentation: Chroen Thani Princess Hotel (Khon Kaen, Thailand)
  • Year and Date: 2008-02-19
• [Presentation] Lack of THP1 protein associated with GANP impairs B cell maintenance (2007)
  • Author(s): Kazuhiko Kuwahara
  • Organizer: 第37回日本免疫学会学術集会
  • Place of Presentation: グランドプリンスホテル新高輪
  • Year and Date: 2007-11-20
• [Presentation] Lack of THP1 protein associated with GANP impairs B cell maintenance (2007)
  • Author(s): Kuwahara K.
  • Organizer: 日本免疫学会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-20
• [Presentation] Characterization of ganp gene abnormality in human breast cancer (2007)
  • Author(s): Kazuhiko Kuwahara
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-03
• [Presentation] 非遺伝性散発性乳癌における胚中心関連GANP分子の発現異常 (2007)
  • Author(s): 桑原一彦
  • Organizer: 第11回基盤的癌免疫研究会
  • Place of Presentation: 東京大学鉄門記念講堂
  • Year and Date: 2007-07-11
• [Presentation] 非遺伝性散発性乳癌におけるGANPの発現異常 (2007)
  • Author(s): 桑原一彦
  • Organizer: 第11回がん分子標的治療研究会
  • Place of Presentation: 大阪国際交流センター
  • Year and Date: 2007-07-06
• [Remarks] 日本語総説(1)桑原一彦、吉田尊、阪口薫雄胚中心B細胞に発現するGANPの遺伝子修復活性、臨床免疫・アレルギー科、51(2) : 119-124 (2009)
• [Patent(Industrial Property Rights)] 胆管がん特異的糖鎖エピトープを認識するモノクローナル抗体 (2009)
  • Inventor(s): 阪口薫雄、桑原一彦、荒木令江、坂本珠美
  • Industrial Property Rights Holder: 財団法人くまもとテクノ産業財団
  • Industrial Property Number: 2009-025607
  • Filing Date: 2009-02-02