Alternative DNA repair pathways of DNA damage induced by topoisomerase inhibitor

• Project/Area Number: 25281018
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Osaka University
• Principal Investigator: Kuraoka Isao 大阪大学, 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): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000); Fiscal Year 2015: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2014: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2013: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
• Keywords: トポイソメラーゼ阻害剤 / 癌 / DNA修復 / ヌクレアーゼ / がん

Outline of Final Research Achievements

Human topoisomerase inhibitors are effective against a broad spectrum of tumors. They induce DNA damage leading cell death by the inhibition of enzymatic topoisomerase reaction specifically.
Here, we studied the repair mechanism of topoisomerase-induced DNA damage in human cells. We found that ERCC1-XPF and RPA participates in DNA repair of the Top1-DNA damage complex and that FEN1 participates in repair of the 5'-phosphotyrosyl terminus of DNA single-strand breaks. Our data provided insights into the DNA repair mechanisms in tumor cells.

Research Products

• [Journal Article] FEN1 participates in repair of the 5'-phosphotyrosyl terminus of DNA single-strand breaks. (2016)
  • Author(s): Kametani Y, Takahata C, Narita T, Tanaka K, Iwai S, Kuraoka I.
  • Journal Title: Carcinogenesis Volume: 37 Issue: 1 Pages: 56-62
  • DOI: 10.1093/carcin/bgv159
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Epigenetic modifications in DNA could mimic oxidative DNA damage: A double-edged sword. (2015)
  • Author(s): Ito S, Kuraoka I
  • Journal Title: DNA Repair Volume: 32 Pages: 52-57
  • DOI: 10.1016/j.dnarep.2015.04.013
  • Peer Reviewed
• [Journal Article] Repair synthesis step involving ERCC1-XPF participates in DNA repair of the Top1-DNA damage complex (2015)
  • Author(s): TAKAHATA Chiaki, MASUDA Yuji, TAKEDACHI Arato, TANAKA Kiyoji, IWAI Shigenori, KURAOKA Isao
  • Journal Title: Carcinogenesis Volume: 36 Issue: 8 Pages: 841-851
  • DOI: 10.1093/carcin/bgv078
  • Peer Reviewed
• [Journal Article] An in vitro method for detecting genetic toxicity based on inhibition of RNA synthesis by DNA lesions (2015)
  • Author(s): Yuina Sonohara, Shigenori Iwai and Isao Kuraoka
  • Journal Title: Genes and Environment Volume: 37 Issue: 1 Pages: 8-8
  • DOI: 10.1186/s41021-015-0014-8
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Diversity of Endonuclease V: From DNA Repair to RNA Editing. (2015)
  • Author(s): Kuraoka I
  • Journal Title: Biomolecules Volume: 5 Issue: 4 Pages: 2194-2206
  • DOI: 10.3390/biom5042194
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Bisnaphthalimidopropyl diaminodicyclohexylmethane induces DNA damage and repair instability in triple negative breast cancer cells via p21 expression. (2015)
  • Author(s): Barron GA, Goua M, Kuraoka I, Bermano G, Iwai S, Kong Thoo Lin P.
  • Journal Title: Chem Biol Interact Volume: 242 Pages: 307-315
  • DOI: 10.1016/j.cbi.2015.10.017
  • Peer Reviewed
• [Journal Article] The SLX4 complex is a SUMO E3 ligase that impacts on replication stress outcome and genome stability. (2015)
  • Author(s): Guervilly JH, Takedachi A, Naim V, Scaglione S, Chawhan C, Lovera Y, Despras E, Kuraoka I, Kannouche P, Rosselli F, Gaillard PH.
  • Journal Title: Mol Cell. Volume: 57 Issue: 1 Pages: 123-137
  • DOI: 10.1016/j.molcel.2014.11.014
  • Peer Reviewed
• [Journal Article] An RNA synthesis inhibition assay for detecting toxic substances using click chemistry. (2014)
  • Author(s): Kametani Y, Iwai S, Kuraoka I.
  • Journal Title: J Toxicol Sci. Volume: 39 Pages: 293-299
  • NAID: 130004903991
  • Peer Reviewed
• [Journal Article] Guanine-5-carboxylcytosine base pairs mimic mismatches during DNA replication. (2014)
  • Author(s): Shibutani T, Ito S, Toda M, Kanao R, Collins LB, Shibata M, Urabe M, Koseki H, Masuda Y, Swenberg JA, Masutani C, Hanaoka F, Iwai S, Kuraoka I
  • Journal Title: Scientific Reports Volume: 4 Issue: 1 Pages: 5220-5220
  • DOI: 10.1038/srep05220
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Fluorescence detection of cellular nucleotide excision repair of damaged DNA. (2014)
  • Author(s): Toga, T., Kuraoka, I., Watanabe, S., Nakano, E., Takeuchi, S., Nishigori, C., Sugasawa, K. and Iwai, S.
  • Journal Title: Scientific Reports Volume: 4 Issue: 1 Pages: 5578-5578
  • DOI: 10.1038/srep05578
  • Peer Reviewed / Open Access
• [Journal Article] Frequencies of mutagenic translesion DNA synthesis over cisplatin-guanine intra-strand crosslinks in lacZ plasmids propagated in human cells (2014)
  • Author(s): Yoshihiro Fujikawa, Masanobu Kawanishi, Isao Kuraoka, Takashi Yagi
  • Journal Title: Mutat Res Genet Toxicol Environ Mutagen Volume: 770 Pages: 23-28
  • DOI: 10.1016/j.mrgentox.2014.05.006
  • Peer Reviewed
• [Journal Article] Human endonuclease V is a ribonuclease specific for inosine-containing RNA. (2013)
  • Author(s): Morita Y, Shibutani T, Nakanishi N, Nishikura K, Iwai S, Kuraoka I.
  • Journal Title: Nat Commun. Volume: 4
  • Peer Reviewed
• [Journal Article] A transfection reporter for the prevention of false-negative results in molecular beacon experiments. (2013)
  • Author(s): Toga T, Kuraoka I, Yasui A, Iwai S.
  • Journal Title: Anal Biochem. Volume: 440 Pages: 9-11
  • Peer Reviewed
• [Journal Article] Strand breakage of a (6-4) photoproduct-containing DNA at neutral pH and its repair by the ERCC1-XPF protein complex. (2013)
  • Author(s): Arichi N, Yamamoto J, Takahata C, Sano E, Masuda Y, Kuraoka I, Iwai S.
  • Journal Title: Org Biomol Chem. Volume: 11 Pages: 3526-3534
  • Peer Reviewed
• [Presentation] Function of Human Endonuclease V: From DNA to RNA (2016)
  • Author(s): Kuraoka I
  • Organizer: The Gordon Research Conference DNA damage, Mutation & Cancer
  • Place of Presentation: ベンチュラ（米国）
  • Year and Date: 2016-03-12
  • Int'l Joint Research / Invited
• [Presentation] ヒトエンドヌクレアーゼ VはRNA修復に関与する。 (2015)
  • Author(s): 倉岡功
  • Organizer: 日本分子生物学会第３８大会
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市）
  • Year and Date: 2015-12-01
• [Presentation] メチルシトシンの酸化体におけるDNA障害 (2015)
  • Author(s): 倉岡功
  • Organizer: 日本環境変異原学会第４４大会
  • Place of Presentation: 九州大学（福岡県福岡市）
  • Year and Date: 2015-11-27
  • Invited
• [Presentation] A NER synthesis step involving ERCC1-XPF participates in DNA repair of the TOPI-DNA complex (2015)
  • Author(s): Kuraoka I
  • Organizer: Structure-Specific Endonucleases in Genome Stability Meeting
  • Place of Presentation: ブルノ（チェコ共和国）
  • Year and Date: 2015-11-04
  • Int'l Joint Research
• [Presentation] ヒトDNAエンドヌクレアーゼVは、イノシンを含むRNAを切断するリボヌクレアーゼである。 (2015)
  • Author(s): 倉岡功
  • Organizer: 日本遺伝学会第８７大会
  • Place of Presentation: 東北大学（宮城県仙台市）
  • Year and Date: 2015-09-25
  • Invited
• [Presentation] A nucleotide excision repair synthesis step involving ERCC1-XPF endonuclease participates in repair of the topoisomerase I-DNA complex (2015)
  • Author(s): Kuraoka I
  • Organizer: Zing Conferences - Genomic Integrity
  • Place of Presentation: ケアンズ（オーストラリア）
  • Year and Date: 2015-08-01
  • Int'l Joint Research / Invited
• [Presentation] ヒトEndonuclease Vにおけるイノシン化RNA切断活性の機能解析 (2015)
  • Author(s): Kim Jungin、岩井成憲、倉岡功
  • Organizer: 日本RNA学会第１５回年会
  • Place of Presentation: ホテルライフォート札幌（北海道札幌市）
  • Year and Date: 2015-07-15
• [Presentation] Epigenetic DNA modification5-carboxylcytosine forms G•T mismatch mimicking-base pairs and induces an apoptosis via MMR (2014)
  • Author(s): 倉岡 功
  • Organizer: 4th Asian Conference on Environmental Mutagens
  • Place of Presentation: インド
  • Year and Date: 2014-12-10 – 2014-12-12
  • Invited
• [Presentation] メチルシトシン酸化誘導体が導く複製機構の障害 (2014)
  • Author(s): 倉岡 功、渋谷 敏博、 岩井 成憲
  • Organizer: 日本環境変異原学会第43回大会
  • Place of Presentation: 東京
  • Year and Date: 2014-12-04 – 2014-12-05
• [Presentation] 5-メチルシトシンとその酸化誘導体における複製システムの統合的理解 (2014)
  • Author(s): 倉岡 功
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-15 – 2014-10-18
  • Invited
• [Presentation] 5-メチルシトシンの酸化誘導体における複製システムの障害 (2014)
  • Author(s): 倉岡 功
  • Organizer: 日本放射線影響学会第57回大会
  • Place of Presentation: 鹿児島
  • Year and Date: 2014-10-01 – 2014-10-03
• [Presentation] ヒトEndonuclease VはiRNA切断酵素である (2014)
  • Author(s): 倉岡 功
  • Organizer: 第16回日本RNA学会年会
  • Place of Presentation: 名古屋
  • Year and Date: 2014-06-23 – 2014-06-25
• [Presentation] FLJ 35220 protein, a human homolog of DNA endonuclease V,is a ribonuclease specific for inosine-containing RNA (2014)
  • Author(s): 倉岡 功
  • Organizer: International Symposium on XP & Related Diseases
  • Place of Presentation: 神戸
• [Presentation] ヒトエンドヌクレアーゼVの機能解析 (2013)
  • Author(s): 倉岡 功
  • Organizer: 日本放射線影響学会第56回大会
  • Place of Presentation: 青森
  • Invited