Molecular research of non-histone lysine methylation in cancer epigenome and its potential as a therapeutic target

• Project/Area Number: 26430116
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Osaka University (2015-2016); Kyushu University (2014)
• Principal Investigator: WATANABE SUGIKO 大阪大学, 微生物病研究所, 准教授 (10433012)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: DNA損傷修復応答 / クロマチン / がん / エピジェネティクス / DNA損傷応答

Outline of Final Research Achievements

A variety of epigenetic changes occur early in carcinogenesis in parallel with genetic mutations and represent in cancer development. The cancer epigenome is regulated by many kinds of factors, such as DNA methylation, chromatin factors and their posttranslational modification, while these precise molecular mechanisms are largely unknown.
In this research, I focused on lysine methylation, which is important for chromatin dynamics in DNA damage response, and analyzed their biological function aiming to control the cellular sensitivity against anti-cancer reagents. I have identified lysine methyltransferases that are required for proper recruitment of repair factors on damaged chromatin and clarified their molecular mechanisms. These molecules potentially present new opportunities for deriving therapeutic strategies for cancer.

Research Products

• [Journal Article] The impact of SASP and its potential as a therapeutic target for senescence-associated diseases. (2017)
  • Author(s): Watabnabe, S., Kawamoto, S., Ohtani, N., & Hara, E.
  • Journal Title: Cancer Science Volume: - Issue: 4 Pages: 563-569
  • DOI: 10.1111/cas.13184
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Phosphorylation of EB2 by Aurora B and CDK1 ensures mitotic progression and genome stability. (2016)
  • Author(s): Iimori M, Watanabe S, Kiyonari S, Matsuoka K, Sakasai R, Saeki H, Oki E, Kitao H, Maehara Y:
  • Journal Title: Nature Communications Volume: [Epub ahead of print] Issue: 1 Pages: 11117-11117
  • DOI: 10.1038/ncomms11117
  • Peer Reviewed / Open Access
• [Journal Article] TOPBP1 regulates RAD51 phosphorylation and chromatin loading and determines PARP inhibitor sensitivity. (2016)
  • Author(s): Moudry P, Watanabe K, Wolanin KM, Bartkova J, Wassing IE, Watanabe S., Strauss R, Troelsgaard Pedersen R, Oestergaard VH, Lisby M, Andújar-Sánchez M, Maya-Mendoza A, Esashi F, Lukas J, Bartek J
  • Journal Title: J Cell Biol. Volume: 212 Issue: 3 Pages: 281-288
  • DOI: 10.1083/jcb.201507042
  • Peer Reviewed / Int'l Joint Research
• [Presentation] テロメア構成タンパク質修飾とエピゲノム異常の関連性 -DNA損傷に対するクロマチン応答からの解析- (2016)
  • Author(s): 渡邉すぎ子
  • Organizer: 第47回アステラス病態代謝研究会研究報告会
  • Place of Presentation: 東京都千代田区
  • Year and Date: 2016-10-15
• [Presentation] がん・老化細胞の運命決定におけるDNA損傷応答の役割 (2016)
  • Author(s): 渡邉すぎ子
  • Organizer: 第5回浜名湖DNA損傷応答ワークショップ
  • Place of Presentation: 静岡県浜松市
  • Year and Date: 2016-04-04
• [Remarks]
  • URL: http://www.biken.osaka-u.ac.jp/lab/molmicro/research/index.html