Interaction of Rad18 with factors involved in checkpoint regulation

• Project/Area Number: 23510065
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Kumamoto University
• Principal Investigator: TATEISHI Satoshi 熊本大学, 発生医学研究所, 講師 (00227109)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: DNA修復 / チェックポイント / Rad18 / Chk2 / 発がん抑制 / 遺伝子欠損マウス / がん / アポトーシス / 染色体異常 / Cancer / Checkpoint / Postreplication repair / PCNA / 細胞老化 / 損傷乗越え複製 / 損傷トレランス / 複製ストレス

Research Abstract

The Chk2 kinase functions as a tumor suppressor.Chk2 Rad18 double knockout mice showed increased rate of spontaneous spleen lymphoma and UV induced skin tumor formation. To elucidate molecular mechanism how the two gene products maintain genome integrity, we have prepared ES cells from the mice and examined survival, apoptosis, chromosomal aberration and sister chromatid exchange rate following UV irradiation of the cells. While deficiency of Rad18 sensitized the cells against UV irradiation, deficiency of Chk2 conferred resistance on the cells. Deficiency of Chk2 increased chromosomal aberration while it did not have a great effect on SCE rates following UV irradiation. Collectively we surmised that deficiency of Rad18 cause genome instability including DSB while the DSB activate Chk2 to compensate deficiency of Rad18 in damaged cells via elimination of DNA damaged cells from the organisms.

Research Products

• [Journal Article] Two replication fork maintenance pathways fuse inverted repeats to rearrange chromosomes (2013)
  • Author(s): Hu, L., Kim, T. M., Son, M. Y., Kim, S. A., Holland, C. L., Tateishi, S., Kim, D. H., Yew, P. R., Montagna, C., Dumitrache, L. C., Hasty, P
  • Journal Title: Nature Volume: 510 Pages: 569-572
  • Peer Reviewed
• [Journal Article] A non-catalytic role of DNA polymerase η in recruiting Rad18 and promoting PCNA monoubiquitination at stalled replication forks (2013)
  • Author(s): Durando, M., Tateishi, S., Vaziri, C
  • Journal Title: Nucleic Acids Res Volume: 41 Pages: 3079-3093
  • Peer Reviewed
• [Journal Article] A non-catalytic role of DNA polymerase η in recruiting Rad18 and promoting PCNA monoubiquitination at stalled replication forks. (2013)
  • Author(s): 33. Durando, M., Tateishi, S., Vaziri, C.
  • Journal Title: Nucleic Acids Res. Volume: 41 Issue: 5 Pages: 3079-3093
  • DOI: 10.1093/nar/gkt016
  • Peer Reviewed
• [Journal Article] Two replication fork maintenance pathways fuse inverted repeats to rearrange chromosomes. (2013)
  • Author(s): 34. Hu, L., Kim, T. M., Son, M. Y., Kim, S. A., Holland, C. L., Tateishi, S., Kim, D. H., Yew, P. R., Montagna, C., Dumitrache, L. C., Hasty, P.
  • Journal Title: Nature Volume: 501 Issue: 7468 Pages: 569-572
  • DOI: 10.1038/nature12500
  • Peer Reviewed
• [Journal Article] The vital role of pol ζ and REV1 in mutagenic, but not correct, DNA synthesis across benzo [α] pyrene-dG and the recruitment of pol ζ by REV1 to a replication-stalled site (2012)
  • Author(s): Hashimoto, K., Cho, Y., Yang, I., Akagi, J., Ohashi, E., Tateishi, S., Wind, N., Hanaoka, F., Ohmori, H., Moriya, M
  • Journal Title: J. Biol. Chem Volume: 287 Pages: 9613-9622
  • Peer Reviewed
• [Journal Article] Mutations in UVSSA cause UV-sensitive syndrome and impair RNA polymerase IIo processing in transcription-coupled nucleotide-excision repair (2012)
  • Author(s): Nakazawa, Y., Sasaki, K., Mitsutake, N., Matsuse, M., Shimada, M., Ohyama, K., Ito, K., Masuyama, R., Kudo, T., Utani, A., Takenaka, K., Miki, Y., Nardo, T., Stefanini, M., Takahashi, Y., Yamashita, S., Tateishi, S., Lehmann, A., Yoshiura, K., Ogi, T
  • Journal Title: Nat. genet Volume: 44 Pages: 586-592
  • NAID: 120006985586
  • Peer Reviewed
• [Journal Article] The vital role of polymerase ζ and REV1 in mutagenic, but not correct, DNA synthesis across benzo[a]pyrene-dG and recruitment of polymerase ζ by REV1 to replication-stalled site. (2012)
  • Author(s): Hashimoto K
  • Journal Title: J Biol Chem Volume: 287 Issue: 12 Pages: 9613-9622
  • DOI: 10.1074/jbc.m111.331728
  • Peer Reviewed
• [Journal Article] Mutations in UVSSA cause UV-sensitive syndrome and impair RNA polymerase IIo processing in transcription-coupled nucleotide-excision repair (2012)
  • Author(s): Nakazawa Y, Sasaki K, Mitsutake N, Yamashita S, Ogi T, et al
  • Journal Title: Nat Genet Volume: 44(5) Issue: 5 Pages: 586-92
  • DOI: 10.1038/ng.2229
  • NAID: 120006985586
  • Peer Reviewed
• [Journal Article] PCNA ubiquitination is important, but not essential for translesion DNA synthesis in mammalian cells (2011)
  • Author(s): Hendel, A., Krijger, P. H., Diamant, N., Goren, Z., Langerak, P., Kim, J., ReiBner, T., Lee, K. Y., Geacintov, N. E., Carell, T., Myung, K., Tateishi, S., D'Andrea, A., Jacobs, H., Livneh, Z
  • Journal Title: PLoS Genet Volume: (9)
  • Peer Reviewed
• [Journal Article] NBS1 recruits RAD18 via a RAD6-like domain and regulates Pol η-dependent translesion DNA synthesis (2011)
  • Author(s): Yanagihara, H., Kobayashi, J., Tateishi, S., Kato, A., Matsuura, S., Tauchi, H., Yamada, K., Takezawa, J., Sugasawa, K., Masutani, C., Hanaoka, F., Weemaes, C. M., Mori, T., Komatsu, K
  • Journal Title: Mol. Cell Volume: 43 Pages: 788-797
  • NAID: 120003338825
  • Peer Reviewed
• [Journal Article] A novel Rad18 ubiqitin ligase-mediated pathway for repair of camptothecin-induced DNA damage. (2011)
  • Author(s): Tateishi, S
  • Journal Title: Cell Cycle Volume: 10 Pages: 2057-2058
  • Peer Reviewed
• [Journal Article] NBS1 recruits RAD18 via a RAD6-like domain and regulates Pol η-dependent translesion DNA synthesis. (2011)
  • Author(s): 20.Yanagihara, H., Kobayashi, J., Tateishi, S., Kato, A., Matsuura, S., Tauchi, H., Yamada, K., Takezawa, J., Sugasawa, K., Masutani, C., Hanaoka, F., Weemaes, C. M., Mori, T., Komatsu, K.
  • Journal Title: Mol. Cell Volume: 43 Pages: 788-797
  • NAID: 120003338825
  • Peer Reviewed
• [Journal Article] PCNA ubiquitination is important, but not essential for translesion DNA synthesis in mammalian cells. (2011)
  • Author(s): 21.Hendel, A., Krijger, P. H., Diamant, N., Goren, Z., Langerak, P., Kim, J., ReiBner, T., Lee, K. Y., Geacintov, N. E., Carell, T., Myung, K., Tateishi, S. et al.
  • Journal Title: PLoS Genet. Volume: 9
  • Peer Reviewed
• [Presentation] Chk2 and Rad18 concertedly maintain genomic integrity to prevent tumor formation International Conference Replication (2014)
  • Author(s): Tateishi, S
  • Organizer: repair and transcription ; coupling mechanisms and chromatin dynamics for genome integrity
  • Place of Presentation: Kyoto University Clock Tower Centennial Hall, Kyoto, Japan
• [Presentation] Chk2 and Rad18 concertedly maintain genomic integrity to prevent tumor formation (2014)
  • Author(s): Tateishi, S.
  • Organizer: International Conference Replication, repair and transcription; coupling mechanisms and chromatin dynamics for genome integrity
  • Place of Presentation: 京都大学時計台記念ホール
  • Invited
• [Presentation] Chk2 and Rad18 contribute cooperatively to maintain genomic stability, leading to prevention of tumorigenesus and germ cells maintenance (2013)
  • Author(s): Tanoue, Y., Tateishi, S
  • Organizer: 29th RBC-NIRS INTERNATIONAL SYMPOSIUM
  • Place of Presentation: コープ京都 Kyoto, Japan
• [Presentation] Chk2 and Rad18 contribute cooperatively to maintain genomic stability, leading to prevention of tumorigenesus and germ cells maintenance. (2013)
  • Author(s): Tanoue, Y., Tateishi, S.
  • Organizer: 29th RBC-NIRS INTERNATIONAL SYMPOSIUM
  • Place of Presentation: コープ京都
  • Invited
• [Presentation] Rad18 contributes to prevention of UV-induced skin cancer and senescence in testis (2012)
  • Author(s): Tanoue, Y., Takamori, S., Tateishi, S
  • Organizer: 28th RBC-NIRS INTERNATIONAL SYMPOSIUM
  • Place of Presentation: コープ京都 Kyoto, Japan
• [Presentation] Rad18 contributes to prevention of tumorigenesis (2012)
  • Author(s): Tanoue, Y., Takamori, S., Tateishi, S
  • Organizer: 28th RBC-NIRS INTERNATIONAL SYMPOSIUM
  • Place of Presentation: コープ京都 Kyoto, Japan
• [Presentation] Loss of Rad18 alleles suppresses tumorigenesis in p53-null mice via cellular senescence (2012)
  • Author(s): Tateishi, S
  • Organizer: Gordon conference
  • Place of Presentation: Ventura, U.S.A.
• [Presentation] Rad18とChk2の連携作用による、細胞老化の抑制およびゲノムの維持機構の解析 (2012)
  • Author(s): 田上 友貴、高森 秀平、奥村 克純、立石 智
  • Organizer: 日本分子生物学会 第35回大会
  • Place of Presentation: マリンメッセ福岡
• [Presentation] 生殖幹細胞のDNA損傷ストレス応答とアポトーシス制御の解析 (2012)
  • Author(s): 21. 伊豫田 奈津子、原田 皆実、谷川 聖佳、立石 智、福尾 恵介、蓬田 健太郎
  • Organizer: 日本分子生物学会 第35回大会
  • Place of Presentation: マリンメッセ福岡
• [Presentation] Loss of Rad18 alleles suppresses tumorigenesis in p53-null mice via cellular senescence (2012)
  • Author(s): Tateishi, S.
  • Organizer: Gordon conference DNA Damage, Mutation & Cancer(招待講演)
  • Place of Presentation: Ventura, U.S.A.
• [Presentation] Rad18 is required for double-stranded break repair and long-term spermatogenesis (2011)
  • Author(s): Tateishi, S., Watanabe, K., Sun, J., Iwabuchi, K., Yomogida, K
  • Organizer: The 34^<th> annual meeting of the molecular biology society of Japan, Workshop
  • Place of Presentation: パシフィコ横浜 Yokohama, Japan
• [Presentation] Rad18 is required for double-stranded break repair and long-term spermatogenesis (2011)
  • Author(s): Tateishi, S., Watanabe, K., Sun, J., Iwabuchi, K., Yomogida, K.
  • Organizer: The 34th annual meeting of the molecular biology society of Japan, Workshop(招待講演)
  • Place of Presentation: 横浜市
• [Book] Regulation of Y-Family Translesion Synthesis (TLS) DNA polymerases by RAD18, In Translesion DNA polymerases : from DNA repair and beyond' Editors : Domenico Maiorano & Dr. Jean-Sebastian Hoffmann
  • Author(s): Vaziri C, Tateishi S, Yang Y, Greenwalt A
  • Publisher: (in press)(ISBN:978-81-308-0538-2)
• [Remarks] ホームページ等
  • URL: http://www.imeg.kumamoto-u.ac.jp/divisions/cell_genetics/index.html