Genetic interaction between Rad18 and checkpoint factors

• Project/Area Number: 20510053
• 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: Kumamoto University
• Principal Investigator: TATEISHI Satoshi 熊本大学, 発生医学研究所, 講師 (00227109)
• Project Period (FY): 2008 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: Rad18 / Chk2 / チェックポイント / 細胞老化 / Xファミリー複製酵素 / ポリメラーゼμ / ポリメラーゼλ / 電離放射線 / DNA修復 / NHEJ / ユビキチン / 53BP1 / 細胞周期調節 / polymerase X / 放射線 / Ku

Research Abstract

Rad18 is required for long-term maintenance of spermatogenesis in mouse testes. We prepared fibroblasts from Chk2-Rad18 double knockout mice. The cells grew very slowly and exhibited cellular senescence. The Cdk inhibitors such as p16, p21 and p53 proteins were highly expressed in the cells. Many RPA protein foci were observed in the nuclei of the cells, thus we inferred that loss of Chk2 and Rad18 resulted in activation of ATR pathway and expression of Cdk inhibitors leading to low cellular growth and senescence.

Research Products

• [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-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
  • 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] Rad18-mediated translesion synthesis of bulky DNA adducts is coupled to activation of the Fanconi anemia DNA repair pathway (2010)
  • Author(s): Song, I.Y., et al
  • Journal Title: J.Biol.Chem. Volume: 285 Pages: 31525-31536
  • Peer Reviewed
• [Journal Article] Phosphorylated Rad 18 directs DNA Polymerase η to sites of stalled replication (2010)
  • Author(s): Day, T.A., et al
  • Journal Title: J.Cell Biol. Volume: 191 Pages: 953-966
  • Peer Reviewed
• [Journal Article] RAD18 promotes DNA double-strand break repair during G1 phase through chromatin retention of 53BP1 (2009)
  • Author(s): Watanabe, K., et al.
  • Journal Title: Nucleic Acids Res. 37 Pages: 2176-2193
  • Peer Reviewed
• [Journal Article] Rad 18 is required for long-term maintenance of spermatogenesis in mouse testes (2009)
  • Author(s): Sun, J., et al.
  • Journal Title: Mech.Dev. 126 Pages: 173-183
  • Peer Reviewed
• [Journal Article] Physical and functional interaction between WRNIP1 and RAD18 (2009)
  • Author(s): Yoshimura, A., et al.
  • Journal Title: Genes Genet.Syst. 84 Pages: 171-178
  • Peer Reviewed
• [Journal Article] Rad18 is required for long-term maintenance of spermatogenesis in mouse (2009)
  • Author(s): Sun, J., et al.
  • Journal Title: Mech. Dev. 126 Pages: 173-183
  • Peer Reviewed
• [Journal Article] RAD18 promotes DNA double-strand break repair during G1 phase through chromatin retention of 53BP1. (2009)
  • Author(s): Watanabe K., et al.
  • Journal Title: Nucleic Acids Res. 37 Pages: 2176-2193
  • Peer Reviewed
• [Journal Article] Recognition of forked and single-stranded DNA structures by human RAD18 complexed with RAD6B protein triggers its recruitment to stalled replication (2008)
  • Author(s): Tsuji, Y., et al.
  • Journal Title: Genes to Cells 13 Pages: 343-354
  • Peer Reviewed
• [Journal Article] The vital role of polζand REV1 in mutagenic, but not correct, DNA synthesis across benzo[・] pyrene-dG and the recruitment of polζby REV1 to a replication-stalled site
  • 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: (In press)
  • Peer Reviewed
• [Journal Article] Exome sequencing identifies KIAA1530 as the causal gene for UV sensitive syndrome complementation group A(UVsS-A)
  • 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: (In press)
  • Peer Reviewed
• [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
  • 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: 第34回日本分子生物学会年会ワークショップMolecular mechnism of replication fork recovery pathways
  • Place of Presentation: 横浜市パシフィコ横浜
• [Presentation] Rad18ノックアウトマウスの自然発癌の形成 (2010)
  • Author(s): 立石智、江藤瑞菜
  • Organizer: 日本放射線影響学会第53回大会
  • Place of Presentation: 京都市
• [Presentation] Rad18 regulates DNA damage tolerance via interaction with polymerase η and monoubiquitination of PCNA (2010)
  • Author(s): Tateishi, S.
  • Organizer: International conference on radiation and cancer biology at Nagasaki 2010
  • Place of Presentation: Nagasaki University(長崎)
• [Presentation] Role of Radl8 in spermatogenesis (2009)
  • Author(s): 立石 智
  • Organizer: Gordon conference Mammali an repair
  • Place of Presentation: Ventura USA
  • Year and Date: 2009-02-10
• [Remarks]
  • URL: http://www.imeg.kumamoto-u.ac.jp/divisions/cell_genetics/index.html
• [Remarks]
  • URL: http://www.imeg.kumamoto-u.ac.jp/en/divisions/Cell_Genetics/index.html
• [Remarks]
  • URL: http://www.cockayneresearchcare.jp/idea/journal5.html
• [Remarks]
  • URL: http://www.imeg.kumamoto-u.ac.jp/divisions/cell_genetics/index.html
• [Remarks]
  • URL: http://www.imeg.kumamoto-u.ac.jp/divisions/cell_genetics/index.html
• [Remarks]
  • URL: http://www.imeg.kumamoto-u.ac.jp/divisions/cell_genetics/index.html