Investigation of DNA replication restart mediated by MUS81-EME1 structure-specific endonuclease, RecQ helicases, and others.

• Project/Area Number: 25710010
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Oita University
• Principal Investigator: HANADA Katsuhiro 大分大学, 医学部, 助教 (90581009)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥25,870,000 (Direct Cost: ¥19,900,000、Indirect Cost: ¥5,970,000); Fiscal Year 2015: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000); Fiscal Year 2014: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000); Fiscal Year 2013: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
• Keywords: ゲノム不安定性 / DNA修復 / 組換え / 染色体不安定性 / 分子生物学

Outline of Final Research Achievements

In our daily life, various DNA stresses inhibit the progression of DNA replications. Remained unreplicated regions on chromosomes often cause chromosomal instabilities. Therefore, the repair of stalled DNA replication is crucial for maintenance of genome integrity. Previously, we have shown that MUS81-EME1 structure-specific endonuclease is involved in the restart mechanism. Here we have identified a new factor involved in the restart mechanism of DNA replication. FBH1 is the DNA helicase in which contains the F-box domain. DNA unwinding activity of FBH1 encouraged the dissociation of RAD51 from DNAs, and the F-box domain of FBH1 was required for the ubiquitin ligase activity. Indeed, FBH1 was involved in the ubiquitination of RAD51. Here we report the new functions of FBH1, contributing the restart mechanism of DNA replication.

Research Products

• [Int'l Joint Research] Erasmus Medical Center/Vrije University Medical Center(オランダ)
• [Int'l Joint Research] University of Copenhagen(デンマーク)
• [Int'l Joint Research] University of Oxford(英国)
• [Int'l Joint Research] Baylor College of Medicine(米国)
• [Journal Article] Mechanisms of gene targeting in higher eukaryotes. (2016)
  • Author(s): Tokunaga A, Anai H, Hanada K.
  • Journal Title: Cellular and Molecular Life Sciences Volume: 73(3) Issue: 3 Pages: 523-533
  • DOI: 10.1007/s00018-015-2073-1
  • Peer Reviewed
• [Journal Article] Mechanisms of interstrand DNA crosslink repair and human disorders. (2016)
  • Author(s): Hashimoto S, Anai H, Hanada K
  • Journal Title: Genes. Environ Volume: 印刷中
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 2重鎖切断修復機構としての相同組換え (2016)
  • Author(s): 花田克浩
  • Journal Title: 生物工学会誌 Volume: 印刷中
• [Journal Article] Multiple malignant changes and recurrent infections in the skin associated with long-term exposure to ultraviolet light and topical psoralen plus ultraviolet A therapy. (2015)
  • Author(s): Hirose-Matsuda H, Okamoto O, Sakai T, Ito A, Kai Y, Hatano Y, Hanada K, Yamaoka Y, Fujiwara S
  • Journal Title: J Dermatol Volume: 42 Issue: 5 Pages: 536-537
  • DOI: 10.1111/1346-8138.12835
  • Peer Reviewed
• [Journal Article] FBH1 influences DNA replication fork stability and homologous recombination through ubiquitylation of RAD51. (2015)
  • Author(s): Chu WK, Payne MJ, Beli P, Hanada K, Choudhary C, Hickson ID
  • Journal Title: Nature Commun. Volume: 6 Issue: 1 Pages: 5931-5931
  • DOI: 10.1038/ncomms6931
  • Peer Reviewed
• [Journal Article] Helicobacter pylori infection introduces DNA double-strand breaks in host cells (2014)
  • Author(s): Hanada K, Uchida T, Tsukamoto Y, Watada M, Yamaguchi N, Yamamoto K, Shiota S, Moriyama M, Graham DY, Yamaoka Y
  • Journal Title: Infect Immun. Volume: 82 Issue: 10 Pages: 4182-4189
  • DOI: 10.1128/iai.02368-14
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Genetic battle between Helicobacter pylori and humans. The mechanism underlying homologous recombination in bacteria, which can infect human cells. (2014)
  • Author(s): Hanada K, Yamaoka Y
  • Journal Title: Microbes Infect Volume: 16 Issue: 10 Pages: 833-839
  • DOI: 10.1016/j.micinf.2014.08.001
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] FBH1 helicase disrupts RAD51 filaments in vitro and modulates homologous recombination in mammalian cells. (2013)
  • Author(s): Simandlova J, Zagelbaum J, Payne MJ, Chu WK, Shevelev I, Hanada K, Chatterjee S, Reid DA, Liu Y, Janscak P, Rothenberg E, Hickson ID.
  • Journal Title: Journal of Biological Chemistry Volume: 288 Issue: 47 Pages: 34168-34180
  • DOI: 10.1074/jbc.m113.484493
  • Peer Reviewed
• [Presentation] 相同組換えを介したDNA複製の再スタート機構の解析 (2015)
  • Author(s): 花田克浩、川島友莉
  • Organizer: 第38回日本分子生物学会
  • Place of Presentation: 神戸市 神戸ポートピアホテル
  • Year and Date: 2015-12-01
  • Invited
• [Patent(Industrial Property Rights)] DNA損傷型物質のスクリーニング方法 (2014)
  • Inventor(s): 花田克浩、川島友莉、西田欣広、山岡吉生
  • Industrial Property Rights Holder: 花田克浩、川島友莉、西田欣広、山岡吉生
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2014-244935
  • Filing Date: 2014-12-03