How do mutations in the XPD result in different skin cancer susceptibilities in patients with xeroderma pigmentosum or trichothiodystrophy?

• Project/Area Number: 20591324
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: Nara Medical University
• Principal Investigator: MORI Toshio Nara Medical University, 医学部, 研究教授 (10115280)
• Co-Investigator(Kenkyū-buntansha): IWAMOTO Takaaki 奈良県立医科大学, 医学部, 博士研究員 (20448773)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 皮膚発がん / 色素性乾皮症 / 硫黄欠乏性毛髪発育異常症 / 紫外線 / XPD / TFIIH / ヌクレオチド除去修復 / ピリミジンニ量体 / 硫黄欠乏性毛髮発育異常症 / ピリミジン二量体

Research Abstract

We studied how mutations in the XPD gene result in different skin cancer susceptibilities in patients with xeroderma pigmentosum (XP) or trichothiodystrophy (TTD). XP-D and TTD cells were both deficient in the repair of UV-induced DNA damage because of helicase activity defects of TFIIH. Since TFIIH also acts as a coactivator, TTD-specific decrease in TFIIH content possibly results in transcriptional defects, which might be implication for the lack of increased incidence of skin cancers in TTD patients.

Research Products

• [Journal Article] Cyclosporin A, but not everolimus, inhibits DNA repair mediated by calcineurin : implications for tumorigenesis under immunosuppression. (2011)
  • Author(s): K.M.Thoms, et al
  • Journal Title: Exp.Dermatol. Volume: 20 Pages: 232-236
  • Peer Reviewed
• [Journal Article] Quantitative detection of 4-hydroxyequilenin-DNA adducts in mammalian cells using an immunoassay with a novel monoclonal antibody. (2010)
  • Author(s): Y. Okahashi, T. Iwamoto, N. Suzuki, S. Shibutani, S. Sugiura, S. Itoh, T. Nishiwaki, S. Ueno, T. Mori.
  • Journal Title: Nucleic Acids Res 38
  • Peer Reviewed
• [Journal Article] Influences of p53 deficiency on the apoptotic response, DNA damage removal and mutagenesis in UVB-exposed mouse skin. (2010)
  • Author(s): H. Ikehata, R. Okuyama, E. Ogawa, S. Nakamura, A. Usami, T. Mori, K. Tanaka, S. Aiba, T. Ono
  • Journal Title: Mutagenesis 25 Pages: 397-405
  • Peer Reviewed
• [Journal Article] Proteolytic fragmentation and sugar chains of plasma ADAMTS13 purified by a conformation- dependent monoclonal antibody. (2010)
  • Author(s): H. Hiura, T. Matsui, M. Matsumoto, Y. Hori, A. Isonishi, S. Kato, T. Iwamoto, T. Mori, Y. Fujimura
  • Journal Title: J.Biochem 148 Pages: 403-4011
  • NAID: 10027878689
  • Peer Reviewed
• [Journal Article] Influences of p53 deficiency on the apoptotic response, DNA damage removal and mutagenesis in UVB-exposed mouse skin. (2010)
  • Author(s): H.Ikehata, et al
  • Journal Title: Mutagenesis Volume: 25 Pages: 397-405
  • Peer Reviewed
• [Journal Article] Quantitative detection of 4-hydroxyequilenin-DNA adducts in mammalian cells using an immunoassay with a novel monoclonal antibody. (2010)
  • Author(s): Y.Okahashi, et al
  • Journal Title: Nucleic Acids Res. Volume: 38
  • Peer Reviewed
• [Journal Article] Protein kinase C gamma, a protein causative for dominant ataxia, negatively regulates nuclear import of recessive-ataxia-related aprataxin. (2009)
  • Author(s): H. Asai, M. Hirano, K. Shimada, T. Kiriyama, Y. Furiya, M. Ikeda, T. Iwamoto, T. Mori, K. Nishinaka, N. Konishi, F. Udaka, S. Ueno
  • Journal Title: Hum Mol Genet 18 Pages: 3533-3543
  • Peer Reviewed
• [Journal Article] Interaction with DNA polymerase eta is required for nuclear accumulation of REV1 and suppression of spontaneous mutations in human cells. (2009)
  • Author(s): J. Akagi, C. Masutani, Y. Kataoka, T. Kan, E. Ohashi, T. Mori, H. Ohmori, F. Hanaoka
  • Journal Title: DNA Repair 8 Pages: 585-599
  • Peer Reviewed
• [Journal Article] The development of a filter to enhance the efficacy and safety of excimer light (308 nm) therapy. (2009)
  • Author(s): K. Kobayashi, Y. Yasuda, Y. Shintani, T. Sumitomo, T. Saga, M. Kimura, A. Yamamoto, T. Mori, A. Maeda, Y. Yamaguchi, A. Morita
  • Journal Title: Photodermatol. Photoimmunol. Photomed 25 Pages: 30-36
  • Peer Reviewed
• [Journal Article] Infrequent mutation of lysophosphatidic acid receptor-1 gene in hamster pancreatic duct adenocarcinomas and established cell lines. (2009)
  • Author(s): T. Tsujiuchi, M. Furukawa, Y. Obo, A. Yamasaki, M. Hotta, C. Kusunoki, N. Suyama, T. Mori, K. Honoki, N. Fukushima
  • Journal Title: J.Toxicol.Pathol 22 Pages: 89-92
  • NAID: 10030977727
  • Peer Reviewed
• [Journal Article] Effect of Prolyl-hydroxyproline (Pro-Hyp), a food-derived collagen peptide in human blood on growth of fibroblasts from mouse skin. (2009)
  • Author(s): Y. Shigemura, K. Iwai, F. Morimatsu, T. Iwamoto, T. Mori, C. Oda, T. Taira, E. Y. Park, Y. Nakamura, K. Sato
  • Journal Title: J Agric Food Chem 57 Pages: 444-449
  • Peer Reviewed
• [Journal Article] Interaction with DNA polymerase eta is required for nuclear accumulation of REV1 and suppression of spontaneous mutations in human cells (2009)
  • Author(s): J.Akagi, et al.
  • Journal Title: DNA Repair 8 Pages: 585-599
  • Peer Reviewed
• [Journal Article] The development of a filter to enhance the efficacy and safety of excimer light(308nm)therapy (2009)
  • Author(s): K.Kobayashi, et al.
  • Journal Title: Photodermatol.Photoimmunol.Photomed. 25 Pages: 30-36
  • Peer Reviewed
• [Journal Article] Protein kinase C gamma, a protein causative for dominant ataxia, negatively regulates nuclear import of recessive-ataxia-related aprataxin (2009)
  • Author(s): H.Asai, et al.
  • Journal Title: Hum Mol Genet. 18 Pages: 3533-3543
  • Peer Reviewed
• [Journal Article] The development of a filter to enhance the efficacy and safety of excimer light (308nm) therapy. (2009)
  • Author(s): K. Kobayashi, et al.
  • Journal Title: Photodermatol. Photoimmunol. Photomed. 25 Pages: 30-36
  • Peer Reviewed
• [Journal Article] Interaction with DNA polymerase eta is required for nuclear accumulation of REV1 and suppression of spontaneous mutations in human cells. (2009)
  • Author(s): J. Akagi, et al.
  • Journal Title: DNA Repair 8 Pages: 585-599
  • Peer Reviewed
• [Journal Article] Comparative study of nucleotide excision repair defects between XPD-mutated fibroblasts derived from trichothiodystrophy and xeroderma pigmentosum patients (2008)
  • Author(s): T. Nishiwaki, N. Kobayashi, T. Iwamoto, A. Yamamoto, S. Sugiura, Y.-C. Liu, A. Sarasin, Y. Okahashi, M. Hirano, S. Ueno, T. Mori
  • Journal Title: DNA Repair 7 Pages: 1990-1998
  • Peer Reviewed
• [Journal Article] Comparative study of nucleotide excision repair defects between XPD-mutated fibrobiasts derived from trichothiodystrophy and xeroderma pigmentosumpatients (2008)
  • Author(s): T. Nishiwaki, et al.
  • Journal Title: DNA Repair 7 Pages: 1990-1998
  • Peer Reviewed
• [Presentation] M期細胞における効率的なDNA修復 (2010)
  • Author(s): 小村潤一郎、池畑広伸、森俊雄、小野哲也
  • Organizer: 日本放射線影響学会第53回大会
  • Place of Presentation: 京都
  • Year and Date: 2010-10-22
• [Presentation] FUS関連筋萎縮側索硬化症細胞の酸化ストレスに対する脆弱性とDNA損傷の蓄積 (2010)
  • Author(s): 平野牧人、池田真徳、殿村恭代、森俊雄、中村雄作、楠進、上野聡
  • Organizer: 日本放射線影響学会第53回大会
  • Place of Presentation: 京都
  • Year and Date: 2010-10-20
• [Presentation] NBS1のDNA損傷トレランス機構の役割 (2010)
  • Author(s): 柳原啓見、森俊雄、立石智、小林純也、小松賢志
  • Organizer: 日本放射線影響学会第53回大会
  • Place of Presentation: 京都
  • Year and Date: 2010-10-20
• [Presentation] Dewar型ピリミジン二量体は熱に不安定である (2010)
  • Author(s): 森俊雄、吉田淳一、岩本顕聡、池畑広伸、小林信彦
  • Organizer: 第32回日本光医学・光生物学会
  • Place of Presentation: 東京
  • Year and Date: 2010-07-31
• [Presentation] 紫外線損傷応答におけるNBS1の新規機能解析 (2009)
  • Author(s): 柳原啓見、森俊雄、立石智、小林純也、小松賢志
  • Organizer: 日本放射線影響学会第52回大会
  • Place of Presentation: 広島
  • Year and Date: 2009-11-12
• [Presentation] ワークショップ「紫外線DNA損傷の修復欠損遺伝病とその分子病態」XPD変異を共通する色素性乾皮症および硫黄欠乏性毛髪発育異常症両患者間でなぜ紫外線皮膚発がん感受性が異なるか (2009)
  • Author(s): 森俊雄
  • Organizer: 日本放射線影響学会第52回大会
  • Place of Presentation: 広島
  • Year and Date: 2009-11-11
• [Presentation] ワークショップ「紫外線DNA損傷の修復欠損遺伝病とその分子病態」DNA単鎖切断修復蛋白アプラタキシンと神経疾患 -常染色体優性・劣性小脳失調症とAAA症候群- (2009)
  • Author(s): 平野牧人、森俊雄、池田真徳、浅井宏英、桐山敬生、降矢芳子、上野聡
  • Organizer: 日本放射線影響学会第52回大会
  • Place of Presentation: 広島
  • Year and Date: 2009-11-11
• [Presentation] XPD変異を共通する色素性乾皮症および硫黄欠乏性毛髪発育異常症両患者間でなぜ紫外線皮膚発がん感受性が異なるか? (2009)
  • Author(s): 森俊雄
  • Organizer: 日本放射線影響学会第52回大会
  • Place of Presentation: 広島市南区民文化センター
  • Year and Date: 2009-11-11
• [Presentation] 紫外線誘発 Dewar型ピリミジン二量体を認識するモノクローナル抗体の樹立と応用 (2009)
  • Author(s): 岩本顕聡、岡橋友美子、池畑広伸、小林信彦、森俊雄
  • Organizer: 第31回日本光医学・光生物学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-07-25
• [Presentation] 複製フォークでのNBS1の新規役割 (2008)
  • Author(s): 柳原啓見、松本結実、森俊雄、立石智、小林純也、小松賢志
  • Organizer: 日本放射線影響学会第51回大会
  • Place of Presentation: 北九州
  • Year and Date: 2008-11-20
• [Presentation] トリ細胞におけるミスマッチ修復遺伝子の紫外線損傷修復に対する機能 (2008)
  • Author(s): 田野恵三、森俊雄、中村純、荒川央、武田俊一、渡邉正己
  • Organizer: 日本放射線影響学会第51回大会
  • Place of Presentation: 北九州
  • Year and Date: 2008-11-20
• [Presentation] 酸化的DNA損傷修復系への小脳失調原因蛋白アプラタキシンの機能的関与 (2008)
  • Author(s): 平野牧人、浅井宏英、桐山敬生、池田真徳、降矢芳子、森俊雄、安井明、上野聡
  • Organizer: 日本放射線影響学会第51回大会
  • Place of Presentation: 北九州
  • Year and Date: 2008-11-20
• [Presentation] XPD変異を共通する二つの遺伝疾患で紫外線皮膚発がん頻度に大差が生じる機構の解析(1) (2008)
  • Author(s): 森俊雄、西脇知永、岩本顕聡、小林信彦、上野聡
  • Organizer: 第30回日本光医学・光生物学会
  • Place of Presentation: 松江
  • Year and Date: 2008-07-11
• [Presentation] XPり変異を共通する二つの遺伝疾患で紫外線皮膚発がん頻度に大差が生じる機構の解析(1) (2008)
  • Author(s): 森 俊雄ら
  • Organizer: 第30回日本光医学・光生物学会
  • Place of Presentation: 松江
  • Year and Date: 2008-07-11
• [Presentation] Determination of 4-hydroxyequilenin-DNA adducts in tissues from mice treated with conjugated equine estrogens (2008)
  • Author(s): Y.Okahashi, T.Iwamoto, S. Shibutani, S.Ueno, T.Mori
  • Organizer: American Association for Cancer Research
  • Place of Presentation: San Diego, USA
  • Year and Date: 2008-04-14
• [Presentation] XPD変異を共通する二つの遺伝疾患でなぜ紫外線皮膚発がん感受性が異なるか (2008)
  • Author(s): 森俊雄
  • Organizer: 太陽紫外線防御研究委員会第18回シンポジウム
  • Place of Presentation: 大阪
  • Year and Date: 2008-03-14
• [Book] からだと光の事典 (2010)
  • Author(s): 太陽紫外線防御研究会
  • Total Pages: 421
  • Publisher: 朝倉書店
• [Book] からだと光の事典 (2010)
  • Author(s): 太陽紫外線防御研究員会
  • Total Pages: 421
  • Publisher: 朝倉書店
• [Remarks] ホームページ等
  • URL: http://www.naramed-u.ac.jp/~ri/
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  • URL: http://www.naramed-u.ac.jp/~ri/
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  • URL: http://www.naramed-u.ac.jp/~ri/
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  • URL: http://www.naramed-u.ac.jp/~ri/