DNA-damage Checkpoint Response to PhIP-exposure and Translesion DNA Synthesis at PhIP-dG

• Project/Area Number: 19570144
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East
• Principal Investigator: FUKUDA Hirokazu National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East, 研究所及び東病院臨床開発センター・生化学部, 室長 (60300943)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2008: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 遺伝子の情報発現と複製 / DNA 付加体 / 遺伝学 / 核酸 / 癌 / 食品 / 変異

Research Abstract

PhIPは、食肉・魚を加熱調理した際に生成される発がん性物質で、我々の細胞中のDNAと付加体(傷の一種)を形成して変異を誘発することが知られている。PhIPを部位特異的に導入した鋳型DNAを用いて種々のDNA polymeraseによるDNA合成反応の解析を行い、pol d (±PCNA)等の複製polymeraseがこの傷の部位で停止してしまうこと、損傷乗り越えpolymerase のREV1とpol kがこの傷を乗り越えてDNA合成を行うことを見出した。このとき1塩基の飛び越しや誤った塩基の挿入がしばしば起こった。さらに詳細な解析から、PhIPにより変異が導入される分子機構を明らかにした。

Research Products

• [Journal Article] Protein hnRNP A1 and its derivative Up1 unfold quadruplex DNA in the human KRAS promoter : implications for transcription. (2009)
  • Author(s): Paramasivam M, Membrino A, Cogoi S, Fukuda H, Nakagama H, Xodo LE.
  • Journal Title: Nucleic Acids Res. 37 Pages: 2841-2853
  • Peer Reviewed
• [Journal Article] Protein hnRNP A1 and its derivative Up1 unfold quadruplex DNA in the human KRAS promoter : implications for transcription (2009)
  • Author(s): Paramasivam M, Membrino A, Cogoi S, Fukuda H, Nakagama H, Xodo LE.
  • Journal Title: Nucleic Acids Res. 37(印刷中)(Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Elucidation of the mode of interaction in the UP1-telomerase RNA-telomeric DNA ternary complex which serves to recruit telomerase to telomeric DNA and to enhance the telomerase activity. (2008)
  • Author(s): Nagata T, Takada Y, Ono A, Nagata K, Konishi Y, Nukina T, Ono M, Matsugami A, Furukawa A, Fujimoto N, Fukuda H, Nakagama H, Katahira M.
  • Journal Title: Nucleic Acids Res. 36 Pages: 6816-6824
  • Peer Reviewed
• [Journal Article] Induction of multinucleated cells and apoptosis in the PC-3 prostate cancer cell line by low concentrations of polyethylene glycol 1000. (2008)
  • Author(s): Fukuta K, Kohri K, Fukuda H, Watanabe M, Sugimura T, Nakagama H.
  • Journal Title: Cancer Sci. 99 Pages: 1055-1062
  • NAID: 10024006588
  • Peer Reviewed
• [Journal Article] Induction of multinucleated cells and apoptosis in the PC-3 prostate cancer cell line by low concentrations of polyethylene glycol 1000 (2008)
  • Author(s): Fukuta K, Kohri K, Fukuda H, Watanabe M, Sugimura T, Nakagama H.
  • Journal Title: Cancer Sci. 99 Pages: 1055-1062
  • NAID: 10024006588
  • Peer Reviewed
• [Journal Article] Elucidation of the mode of interaction in the UP1-telomerase RNA-telomeric DNA ternary complex which serves to recruit telomerase to telomeric DNA and to enhance the telomerase activity (2008)
  • Author(s): Nagata T, Takada Y, Ono A, Nagata K, Konishi Y, Nukina T, Ono M, Matsugami A, Furukawa A, Fujimoto N, Fukuda H, Nakagama H, Katahira M.
  • Journal Title: Nucleic Acids Res. 36 Pages: 6816-6824
  • Peer Reviewed
• [Journal Article] HnRNP A3 binds to and protects mammalian telomeric repeats in vitro.、Biochem. (2007)
  • Author(s): Tanaka E, Fukuda H, Nakashima K, Tsuchiya N, Seimiya H, Nakagama H.
  • Journal Title: Biophys Res. Commun. 358 Pages: 608-614
  • Peer Reviewed
• [Journal Article] Induction of abnormal nuclear shapes in two distinct modes by overexpression of serine/threonine protein phosphatase 5 in HeLa cells. (2007)
  • Author(s): Fukuda H, Tsuchiya N, Hara-Fujita K, Takagi S, Nagao M, Nakagama H.
  • Journal Title: J. Cell. Biochem. 101 Pages: 321-330
  • Peer Reviewed
• [Presentation] Translesion DNA synthesis at PhIP-dG (2008)
  • Author(s): Fukuda H., Takamura T., Nakagama H.
  • Organizer: 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] Genomic copy number aberrations in N-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN)-induced invasive bladder cancers of mice. (2008)
  • Author(s): Kanemoto K., Fukuta K., Fukuda H., Ochiai M., Kohri K., Sugimura T., Nakagama H.
  • Organizer: 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] Translesion DNA synthesis at PhIP-adducted dG (2007)
  • Author(s): 福田 博政
  • Organizer: 日本分子生物学会・日本生化学会合同大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-12-13
• [Presentation] Translesion DNA synthesis at PhIP-adducted dG. (2007)
  • Author(s): Fukuda H., Takamura T., Seki C.,Nakagama H.
  • Organizer: 日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-12-11
• [Presentation] Translesion DNA synthesis at PhIP-dG adduct (2007)
  • Author(s): Fukuda H., Seki C., Takamura T., Nakagama H.
  • Organizer: 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] Induction of multinucleated cells and apoptosis in the PC-3 prostate cancer cell line by low concentrations of polyethylene glycol 1000. (2007)
  • Author(s): Fukuta K, Kohri K, Fukuda H, Watanabe M, Sugimura T, Nakagama H.
  • Organizer: 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] Translesion DNA synthesis at PhIP-adducted dG (2007)
  • Author(s): 福田 博政
  • 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