Effects of DNA lesions on the transcription reaction of mitochondrial RNA polymerase

• Project/Area Number: 22510060
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Osaka University
• Principal Investigator: KURAOKA Isao 大阪大学, 大学院・基礎工学研究科, 准教授 (60335396)
• Co-Investigator(Renkei-kenkyūsha): IWAI Shigenori 大阪大学大学院, 基礎工学研究科, 教授 (10168544)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ミトコンドリア / RNAポリメラーゼ / 酸化DNA損傷

Research Abstract

Mitochondrial RNA polymerase (mtRNAP) catalyzes the synthesis of essential transcripts in mitochondria where reactive oxidative (ROS) species are generated as byproducts. The occurrence of RNA synthesis by mtRNAP at oxidative DNA lesions remains unknown. Purified mtRNAP and a complex of RNA primer/DNA template containing a single DNA lesion were used for in vitro RNA synthesis assays. We show that mtRNAP bypassed the oxidative DNA lesion.

Research Products

• [Journal Article] Establishment of a human cell line sta bly overexpressing mouse Nip45 and characte rization of Nip45 subcellular localization. (2013)
  • Author(s): Hashiguchi K, Ozaki M, Kuraoka I, Saitoh H
  • Journal Title: Biochem Biophys Res Commun Volume: 430 Pages: 72-72
• [Journal Article] Miscoding properties of 8-ch loro-2′-deoxyguanosine, a hypochlorous aci d-induced DNA adduct, catalysed by huma n DNA polymerases. (2013)
  • Author(s): Sassa A, Kamoshita N, Matsuda T, Ishi i Y, Kuraoka I, Nohmi T, Ohta T, Honma M, Yasui M
  • Journal Title: Mutagenesis Volume: 28 Pages: 81-88
• [Journal Article] Effects of DNA lesions on the transcription reaction of mitochondrial RNA p olymerase: implications for bypass RNA synt hesis on oxidative DNA lesions. (2013)
  • Author(s): Nakanishi N, Fukuoh A, Kang D, Iwai S, Kuraoka I
  • Journal Title: Mutagenesis Volume: 28 Pages: 117-123
• [Journal Article] Establishment of a human cell line stably overexpressing mouse Nip45 and characterization of Nip45 subcellular localization. (2013)
  • Author(s): Hashiguchi K, Ozaki M, Kuraoka I, Saitoh H.
  • Journal Title: Biochem Biophys Res Commun Volume: 430 Pages: 72-77
  • Peer Reviewed
• [Journal Article] Miscoding properties of 8-chloro-2'-deoxyguanosine, a hypochlorous acid-induced DNA adduct, catalysed by human DNA polymerases. (2013)
  • Author(s): Sassa A, Kamoshita N, Matsuda T, Ishii Y, Kuraoka I, Nohmi T, Ohta T, Honma M, Yasui M.
  • Journal Title: Mutagenesis Volume: 28 Pages: 81-88
  • Peer Reviewed
• [Journal Article] Effects of DNA lesions on the transcription reaction of mitochondrial RNA polymerase: implications for bypass RNA synthesis on oxidative DNA lesions. (2013)
  • Author(s): Nakanishi N, Fukuoh A, Kang D, Iwai S, Kuraoka I.
  • Journal Title: Mutagenesis Volume: 28 Pages: 117-123
  • Peer Reviewed
• [Journal Article] Effects of 5',8-cyclodeoxya denosine triphosphates on DNA synthesis. (2012)
  • Author(s): Kamakura N, Yamamoto J, Brooks PJ, Iwa i S, Kuraoka I.
  • Journal Title: Chem Res Toxicol Volume: 25 Pages: 2718-2724
• [Journal Article] Identification of small molecule prolife rating cell nuclear antigen (PCNA) inhibitor that disrupts interactions with PIP-box prot eins and inhibits DNA replication (2012)
  • Author(s): Punchihewa C, Inoue A, Hishiki A, Fuji kawa Y, Connelly M, Evison B, Shao Y, Heath R, Kuraoka I, Rodrigues P, Hashimo to H, Kawanishi M, Sato M, Yagi T, Fujii N
  • Journal Title: J Biol Chem Volume: 287 Pages: 14289-14300
• [Journal Article] Xeroderma p igmentosum group F protein binds to Eg5 and is required for proper mitosis: implicati ons for XP-F and XFE. (2012)
  • Author(s): Tan LJ, Saijo M, Kuraoka I, Narita T, T akahata C, Iwai S, Tanaka K
  • Journal Title: Genes Cells Volume: 17 Pages: 173-185
• [Journal Article] When and Where Polymerase s Encounter DNA lesions (2012)
  • Author(s): Kuraoka I
  • Journal Title: Genes and Envir onment Volume: 34 Pages: 58-62
• [Journal Article] Effects of 5',8-cyclodeoxyadenosine triphosphates on DNA synthesis. (2012)
  • Author(s): Kamakura N, Yamamoto J, Brooks PJ, Iwai S, Kuraoka I.
  • Journal Title: Chem Res Toxicol. Volume: 25 Pages: 2718-2724
  • Peer Reviewed
• [Journal Article] Identification of small molecule proliferating cell nuclear antigen (PCNA) inhibitor that disrupts interactions with PIP-box proteins and inhibits DNA replication. (2012)
  • Author(s): Punchihewa C, Inoue A, Hishiki A, Fujikawa Y, Connelly M, Evison B, Shao Y, Heath R, Kuraoka I, Rodrigues P, Hashimoto H, Kawanishi M, Sato M, Yagi T, Fujii N.
  • Journal Title: J Biol Chem. Volume: 287 Pages: 14289-14300
  • Peer Reviewed
• [Journal Article] Xeroderma pigmentosum group F protein binds to Eg5 and is required for proper mitosis : implications for XP-F and XFE (2012)
  • Author(s): Tan LJ, Saijo M, Kuraoka I, Narita T, Takahata C, Iwai S, Tanaka K
  • Journal Title: Genes Cells Volume: 16 Pages: 173-185
  • Peer Reviewed
• [Journal Article] Identification of a small molecule PCNA inhibitor that disrupts interactions with PIP-Box proteins and inhibits DNA replication (2012)
  • Author(s): Punchihewa C, Inoue A, Hishiki A, Fujikawa Y, Connelly M, Evison B, Shao Y, Heath R, Kuraoka I, Rodrigues P, Hashimoto H, Kawanishi M, Sato M, Yagi T, Fujii N
  • Journal Title: J Biol Chem Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] A method for detecting genetic toxicity using the RN A synthesis response to DNA damage. (2011)
  • Author(s): Morita Y, Iwai S, Kuraoka I
  • Journal Title: JTox icol Sci Volume: 36 Pages: 515-521
• [Journal Article] Mutant Cockayne syn drome group B protein inhibits repair of D NA topoisomerase I-DNA covalent complex. (2011)
  • Author(s): Horibata K, Saijo M, Bay MN, Lan L, Kuraoka I, Brooks PJ, Honma M, Nohmi T, Yasui A, Tanaka K
  • Journal Title: Genes Cells Volume: 16 Pages: 101-114
• [Journal Article] A method for detecting genetic toxicity using the RNA synthesis response to DNA damage (2011)
  • Author(s): Morita Y, Iwai S, Kuraoka I
  • Journal Title: J Toxicol Sci Volume: 5 Pages: 515-521
  • NAID: 10029481056
  • Peer Reviewed
• [Journal Article] Characterization of a Y-family DNA polym erase eta from the eukaryotic thermophile Alvinella pompejana (2010)
  • Author(s): Kashiwagi S, Kuraoka I, Fujiwara Y, Hit omi K, Cheng QJ, Fuss, JO, Shin, DS, Masutani C, Tainer, JA, Hanaoka F, Iwai S
  • Journal Title: J.Nucleic Acids
• [Journal Article] MMXD, a TFIIH-indepen dent XPD-MMS19 protein complex involved in chromosome segregation. (2010)
  • Author(s): Ito S, Tan LJ, Andoh D, Narita T, Seki M, Hirano Y, Narita K, Kuraoka I, Hirao ka Y, Tanaka K
  • Journal Title: Mol Cell Volume: 39 Pages: 632-40
• [Journal Article] A non-isotopic assay uses bromouridine and RNA synthesis to detect DNA damage responses (2010)
  • Author(s): Hasegawa M, Iwai S, Kuraoka I
  • Journal Title: Mutat Res Volume: 699 Pages: 62-66
• [Journal Article] Fluorescent probes for the a nalysis of DNA strand scission in base exc ision repair. (2010)
  • Author(s): atsumoto N, Toga T, Hayashi R, Suga sawa K, Katayanagi K. Ide H, Kuraoka I, Iwai S
  • Journal Title: Nucleic Acids Res Volume: 38
• [Journal Article] Polymerization by D NA polymerase eta is blocked by cis-diam minedichloroplatinum(II) 1,3-d(GpTpG) cros slink: Implications for cytotoxic effects in nucleotide excision repair-negative tumor ce lls. (2010)
  • Author(s): Chijiwa S, Masutani C, Hanaoka F, Iwai S, Kuraoka I
  • Journal Title: Carcinogenesis Volume: 31 Pages: 388-393
• [Journal Article] Fluorescent probes for the analysis of DNA strand scission in base excision repair. (2010)
  • Author(s): Matsumoto N, Toga T, Hayashi R, Sugasawa K, Katayanagi K, Ide H, Kuraoka I, Iwai S
  • Journal Title: Nucleic Acids Res. Volume: 38
  • Peer Reviewed
• [Journal Article] A non-isotopic assay uses bromouridine and RNA synthesis to detect DNA damage responses. (2010)
  • Author(s): Hasegawa M, Iwai S, Kuraoka I.
  • Journal Title: Mutat Res. Volume: 699 Pages: 62-66
  • Peer Reviewed
• [Journal Article] MMXD, a TFIIH-independent XPD-MMS19 protein complex involved in chromosome segregation. (2010)
  • Author(s): Ito S, Tan LJ, Andoh D, Narita T, Seki M, Hirano Y, Narita K, Kuraoka I, Hiraoka Y, Tanaka K
  • Journal Title: Mol.Cell. Volume: 39 Pages: 632-640
  • Peer Reviewed
• [Journal Article] Characterization of a Y-Family DNA Polymerase eta from the Eukaryotic Thermophile Alvinella pompejana. (2010)
  • Author(s): Kashiwagi S, Kuraoka I, Fujiwara Y, Hitomi K, Cheng QJ, Fuss JO, Shin DS, Masutani C, Tainer JA, Hanaoka F, Iwai S.
  • Journal Title: J Nucleic Acids. Pages: 701472-701472
  • Peer Reviewed
• [Journal Article] Mutant Cockayne syndrome group B protein inhibits repair of DNA topoisomerase I-DNA covalent complex. (2010)
  • Author(s): Horibata K, Saijo M, Bay MN, Lan L, Kuraoka I, Brooks PJ, Honma M, Nohmi T, Yasui A, Tanaka K.
  • Journal Title: Genes Cells. Volume: 16 Pages: 101-114
  • Peer Reviewed
• [Presentation] New function of a struc ture-specific nuclease human endonuclea se V (2012)
  • Author(s): Isao Kuraoka
  • Organizer: EMBO workshop Structure-specific nucleases in DNA replication & repair
  • Place of Presentation: Cote DAzur, France
  • Year and Date: 2012-09-18
• [Presentation] ミトコンドリア RNAポリメラーゼ転写反応における酸化 DNA損傷の影響 (2012)
  • Author(s): 倉岡 功
  • Organizer: 日本放射線影響学会
  • Place of Presentation: 仙台
  • Year and Date: 2012-09-07
• [Presentation] New function of human e ndonuclease V (2012)
  • Author(s): Isao Kuraoka
  • Organizer: US-JAPAN DNA repair meet ing
  • Place of Presentation: VIRGINIA, USA
  • Year and Date: 2012-04-12
• [Presentation] New function of human endonuclease V (2012)
  • Author(s): Isao Kuraoka
  • Organizer: US-JAPAN DNA REPAIR MEETING
  • Place of Presentation: VIRGINIA, USA
  • Invited
• [Presentation] New fuction of a structure-specific nuclease human endonuclease V (2012)
  • Author(s): Isao Kuraoka
  • Organizer: EMBO Workshop Structure-specific nucleases in DNA replication & repair
  • Place of Presentation: Cote D’Azur, France
  • Invited
• [Presentation] ミトコンドリアRNAポリメラーゼ転写反応における酸化DNA損傷の影響 (2012)
  • Author(s): 倉岡功
  • Organizer: 日本放射線影響学会第55回大会
  • Place of Presentation: 仙台
• [Presentation] Effects of oxidative DNA les ions on transcription by mitochondria R NA polymerase (2011)
  • Author(s): 倉岡 功
  • Organizer: 第34回大会日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-14
• [Presentation] Effects of oxidative DNA lesions on transcription by mitochondria RNA polymerase (2011)
  • Author(s): 倉岡功
  • Organizer: 第34回大会日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県)(招待講演)
  • Year and Date: 2011-12-14
• [Presentation] ヒトFLJ35220タンパク質の機能解析 (2011)
  • Author(s): 森田陽子、岩井成憲、倉岡功
  • Organizer: 日本環境変異原学会第40回大会
  • Place of Presentation: 東京
  • Year and Date: 2011-11-21
• [Presentation] ヒトFLJ35220タンパク質の機能解析 (2011)
  • Author(s): 森田陽子、岩井成憲、倉岡功
  • Organizer: 日本環境変異原学会第40回大会
  • Place of Presentation: 学術総合センター(東京都)
  • Year and Date: 2011-11-21
• [Presentation] An Assay for Genetic Toxicity using Transcription-Response to Damaged DNA (2010)
  • Author(s): 倉岡 功
  • Organizer: 2nd Asian Conference on Environmental Mutagens
  • Place of Presentation: Pataya, Thai
  • Year and Date: 2010-12-16
• [Presentation] An Assay for Genetic Toxicity using Transcription-Response to Damaged DNA (2010)
  • Author(s): 倉岡功
  • Organizer: 2^<nd> Asian Conference on Environmental Mutagens
  • Place of Presentation: パタヤ(タイ)
  • Year and Date: 2010-12-16
• [Presentation] 損傷 DNAを鋳型にした RNA伸長反応と変異の分子メカニズム (2010)
  • Author(s): 倉岡 功
  • Organizer: 第39回日本環境変異原学会
  • Place of Presentation: 筑波
  • Year and Date: 2010-11-16
• [Presentation] 損傷DNAを鋳型にしたRNA伸長反応と変異の分子メカニズム (2010)
  • Author(s): 倉岡功
  • Organizer: 第39回日本環境変異原学会
  • Place of Presentation: 筑波(招待講演)
  • Year and Date: 2010-11-16
• [Presentation] A cis-Diamminedichloroplatinum (II) 1,3-d(GpTpG) crosslinks blocks polymeriz ation by DNA polymerase h (2010)
  • Author(s): 倉岡 功
  • Organizer: 第37回国際核酸科学シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 2010-11-10
• [Presentation] A cis-Diamminedichloroplatinum(II)1,3-d(GpTpG)crosslinks blocks polymerization by DNA polymerase h (2010)
  • Author(s): 倉岡功
  • Organizer: 第37回国際核酸科学シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 2010-11-10
• [Presentation] RNA合成阻害を用いた non R I-DNA損傷検出系 (2010)
  • Author(s): 倉岡 功
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-22
• [Presentation] RNA合成阻害を用いたnon RI-DNA損傷検出系 (2010)
  • Author(s): 倉岡功
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-22