Interaction of Rad18 with factors involved in checkpoint regulation

2013 Fiscal Year Final Research Report

• 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
• 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

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] 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
  • 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) Pages: e1002262
  • 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
  • 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
  • Year and Date: 20140204-05
• [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
  • Year and Date: 20131128-29
• [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
  • Year and Date: 20121129-30
• [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
  • Year and Date: 20121129-30
• [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.
  • Year and Date: 20120325-30
• [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
  • Year and Date: 20111213-16
• [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