Functional analysis of DNA damage response of transcription factor FOXO1 in lifespan regulation

• Project/Area Number: 22688029
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Applied molecular and cellular biology
• Research Institution: University of Tsukuba
• Principal Investigator: DAITOKU Hiroaki 筑波大学, 生命環境系, 講師 (30361314)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥26,780,000 (Direct Cost: ¥20,600,000、Indirect Cost: ¥6,180,000); Fiscal Year 2012: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000); Fiscal Year 2011: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000); Fiscal Year 2010: ¥13,130,000 (Direct Cost: ¥10,100,000、Indirect Cost: ¥3,030,000)
• Keywords: 老化 / 転写因子 / 紫外線 / DNA損傷修復 / 寿命 / FOXO / 線虫 / 損傷乗り越えDNA複製 / 損傷乗り越え複製 / DNA損傷 / 損傷乗り越え修復

Research Abstract

Transcription factor FOXO1 is known to be involved in lifespan extension and anti-aging; however, the molecular mechanism remains unclear. In this study, we found that FOXO1 contributes to tlanslesion DNA synthesis, which serves as the DNA damage response against ultra violet (UV) irradiation. Furthermore, genetic analysis using C. elegans showed that FOXO1/DAF-16 plays a crucial role in UV resistance during larval development. Our finding will help to elucidate the anti-aging mechanism of FOXO1.

Research Products

• [Journal Article] Conserved SAMS function in regulating egg-laying in C. elegans (2013)
  • Author(s): Tamiya H.
  • Journal Title: J Recept Signal Transduct Res. Volume: 33(1) Issue: 1 Pages: 56-62
  • DOI: 10.3109/10799893.2012.756896
  • Peer Reviewed
• [Journal Article] GSK3β regulates gluconeogenic gene expression through HNF4α and FOXO1 (2012)
  • Author(s): Sakamaki, J., et al
  • Journal Title: J.Recept.Signal Transduct.Res. Volume: 32 Issue: 2 Pages: 96-101
  • DOI: 10.3109/10799893.2012.660531
  • Peer Reviewed
• [Journal Article] GSK3ss regulates gluconeogenic gene expression through HNF4α and FOXO1 (2012)
  • Author(s): Sakamaki J, Daitoku H, et al.
  • Journal Title: J.Recept.Transduct.Res. Volume: 32 Pages: 96-101
  • Peer Reviewed
• [Journal Article] Asymmetric arginine dimethylation determines life span in C.elegans by regulating forkhead transcription factor DAF-16 (2011)
  • Author(s): Takahashi Y., Daitoku H., Hirota K., Tamiya H., Yokoyama A., Kako K., Nagashima Y., Nakamura A., Shimada T., Watanabe S., Yamagata K., Yasuda K., Ishii N., Fukamizu A.
  • Journal Title: Cell Metabolism Volume: 13 Issue: 5 Pages: 505-516
  • DOI: 10.1016/j.cmet.2011.03.017
  • Peer Reviewed
• [Journal Article] Arginine methylation of BCL-2 antagonist of cell death (BAD) counteracts its phosphorylation and inactivation by Akt (2011)
  • Author(s): Sakamaki, J., et al
  • Journal Title: Proc.Natl.Acad.Sci.USA Volume: 108 Issue: 15 Pages: 6085-6090
  • DOI: 10.1073/pnas.1015328108
  • Peer Reviewed
• [Journal Article] Regulation of FoxO transcription factors by acetylation and protein-protein interactions (2011)
  • Author(s): Daitoku, H.Sakamaki, J.Fukamizu, A.
  • Journal Title: Biochim.Biophys.Acta. Volume: 1813 Issue: 11 Pages: 1954-1960
  • DOI: 10.1016/j.bbamcr.2011.03.001
  • Peer Reviewed
• [Journal Article] The C. elegans PRMT-3 possesses a type III protein arginine methyltransferases activity (2011)
  • Author(s): Takahashi Y, Daitoku H, Yokoyama A, Nakayama K, Kim JD, Fukamizu A
  • Journal Title: J.Recept. Signal Transduct Volume: 31 Issue: 2 Pages: 168-172
  • DOI: 10.3109/10799893.2011.555768
  • Peer Reviewed
• [Journal Article] Arginine methylation of BCL-2 antagonist of cell death (BAD) counteracts its phosphorylation and inactivation by Akt (2011)
  • Author(s): Sakamaki, JI.
  • Journal Title: Proc.Natl.Acad.Sci.U.S.A. Volume: 108 Pages: 6085-6090
  • Peer Reviewed
• [Journal Article] Regulation of FoxO transcription factors by acetylation and protein-protein interactions (2011)
  • Author(s): Daitoku, H.
  • Journal Title: Biochem.Biophys.Acta. Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] The C.elegans PRMT-3 possesses a type III protein arginine me thyltransferase activity (2011)
  • Author(s): Takahashi, Y.
  • Journal Title: J.Recept.Signal.Transduct.Res. Volume: 2 Pages: 168-172
  • Peer Reviewed
• [Presentation] 転写因子FOXO1は紫外線DNA損傷応答に関与する (2013)
  • Author(s): 金子悠太、大徳浩照、深水昭吉
  • Organizer: 若手ワークショップ@鬼怒川
  • Place of Presentation: 栃木県日光市
  • Year and Date: 2013-01-24
• [Presentation] 転写因子Foxo1は紫外線DNA損傷応答に関与する (2013)
  • Author(s): 金子悠太
  • Organizer: 転写代謝システム 若手ワークショップ
  • Place of Presentation: ホテル鬼怒川 御苑
• [Presentation] 転写因子Foxo1は紫外線DNA損傷応答に関与する (2012)
  • Author(s): 金子悠太、大徳浩照、深水昭吉
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2012-12-11
• [Presentation] 転写因子Foxo1は紫外線DNA損傷応答に関与する (2011)
  • Author(s): 金子悠太、大徳浩照、深水昭吉
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2011-12-14
• [Presentation] フォークヘッド転写因子DAF-16は線虫の損傷乗り越え複製に関与する (2011)
  • Author(s): 松本佳保里、大徳浩照、深水昭吉
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2011-12-14
• [Presentation] 糖代謝調節における転写因子のクロストークとアルギニンメチル化制御 (2011)
  • Author(s): 大徳浩照
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(招待講演)
  • Year and Date: 2011-09-23
• [Presentation] アルギニンメチル化とAktリン酸化のクロストークは寿命制御に関与する (2011)
  • Author(s): 大徳浩照
  • Organizer: 転写研究会若手シンポジウム
  • Place of Presentation: 東北大学東京分室会議室
  • Year and Date: 2011-02-18
• [Remarks]
  • URL: http://akif2.tara.tsukuba.ac.jp