Role of nucleolin in maintenance of genomic stability through chromatin remodeling

• Project/Area Number: 24310041
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Kyoto University
• Principal Investigator: KOBAYASHI Junya 京都大学, 放射線生物研究センター, 准教授 (30301302)
• Co-Investigator(Kenkyū-buntansha): OKUI Michiyo 桐蔭横浜大学, 先端医用工学センター, 講師 (20327654) ; HAYASHI Ikue 広島大学, 医歯薬保健学研究院, 助教 (00346503)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2012: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
• Keywords: ゲノム不安定性 / nucleolin / クロマチン / DNA損傷 / DNA修復 / ゲノム安定性

Outline of Final Research Achievements

We identified nucleolin (nucleolar protein) as one of H2AX-binding proteins. As nucleolin could remodel chromatin structure at transcription-active sites, we investigated the role of chromatin remodeling radiation-induced DNA damage. Nucleolin-depleted cells remarkably reduced cell cycle checkpoints and HR repair activity, and showed un-stabilization of stalled replication fork and abnormal chromatin remodeling. Therefore, nucleolin could be important to maintain genomic stability through chromatin remodeling.

Research Products

• [Journal Article] Increased oxidative stress in AOA3 cells disturbs ATM-dependent DNA damage responses (2015)
  • Author(s): Kobayashi J, et al.
  • Journal Title: Mutat Res Genet Toxicol Environ Mutagen Volume: 782 Pages: 42-50
  • DOI: 10.1016/j.mrgentox.2015.03.012
  • NAID: 120005670865
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Wilms' tumor gene WT1 promotes homologous recombination- mediated DNA damage repair (2015)
  • Author(s): Oji Y, Kobayashi J, et al.
  • Journal Title: Mol Carcinog Volume: in press Issue: 12 Pages: 1758-71
  • DOI: 10.1002/mc.22248
  • Peer Reviewed / Open Access
• [Journal Article] Role for WRN in Preserving Nascent DNA Strands after Replication Stress (2014)
  • Author(s): Su F, Kobayashi J, et al.
  • Journal Title: Cell Reports Volume: 9 Issue: 4 Pages: 1387-1401
  • DOI: 10.1016/j.celrep.2014.10.025
  • Peer Reviewed / Open Access
• [Journal Article] Hypergonadotropic Hypogonadism and Hypersegmented Neutrophils in a Patient with Ataxia-Telangiectasia-Like Disorder: Potential Diagnostic Clues? (2014)
  • Author(s): Yoshida T, Kobayashi J, et al.
  • Journal Title: Am J Med Genet A Volume: 164A Issue: 7 Pages: 1830-1834
  • DOI: 10.1002/ajmg.a.36546
  • NAID: 120005456013
  • Peer Reviewed / Open Access
• [Journal Article] ATM regulates Cdt1 stability during the unperturbed S phase to prevent re-replication. (2014)
  • Author(s): Iwahori S, Kohmon D, Kobayashi J, Tani Y, Yugawa T, Komatsu K, Kiyono T, Sugimoto N, Fujita M.
  • Journal Title: Cell Cycle Volume: 13 Issue: 3 Pages: 471-481
  • DOI: 10.4161/cc.27274
  • Peer Reviewed / Open Access
• [Journal Article] Mutations in the FHA-domain of ectopically expressed NBS1 lead to Radiosensitization and to no increase in somatic mutation rates via a partial suppression of homologous recombination. (2014)
  • Author(s): Ohara M, Kobayashi J, et al.
  • Journal Title: Journal of Radiation Research Volume: in press
  • Peer Reviewed
• [Journal Article] ATM-mediated phosphorylation of SOG1 is essential for the DNA damage response in Arabidopsis (2013)
  • Author(s): Yoshiyama KO, Kobayashi J. et al.
  • Journal Title: EMBO report Volume: 14 Pages: 817-822
  • NAID: 120006537387
  • Peer Reviewed
• [Journal Article] Role of NBS1 in DNA damage response and its relationship with cancer development (2013)
  • Author(s): Saito Y, Kobayashi J et al.
  • Journal Title: Translational Cancer Research Volume: 2 Pages: 178-189
  • NAID: 120005300469
  • Peer Reviewed
• [Journal Article] Efficient gene targeting by TAL effector nucleases coinjected with exonucleases in zygotes (2013)
  • Author(s): Tomoji Mashimo
  • Journal Title: Scientific Reports Volume: 3 Issue: 1 Pages: 1253-1253
  • DOI: 10.1038/srep01253
  • Peer Reviewed
• [Journal Article] DNA damage sensor MRE11 recognizes cytosolic double-stranded DNA and induces type I interferon by regulating STING traffickining (2013)
  • Author(s): Takeshi Kondo, Junya Kobayashi, Tatusya Saitoh, Kenta Maruyama. Ken J. Ishii, Glen N. Barber, Kenshi、Komatsu, Shizuo Akira, and Taro Kawai
  • Journal Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 110 Issue: 8 Pages: 2969-2974
  • DOI: 10.1073/pnas.1222694110
  • Peer Reviewed
• [Journal Article] Nucleolin participates in DNA double-strand break-induced damage response through MDC1-dependent pathway. (2012)
  • Author(s): Kobayashi J
  • Journal Title: PLoS Qne Volume: 7
  • NAID: 120004996269
  • Peer Reviewed
• [Journal Article] Generation and characterization of severe combined immune deficientrats. (2012)
  • Author(s): Mashimo T, Takizawa A, Kobayashi J, Kunihiro Y, Yoshimi K, Ishida S, Tanabe K, Yanagi A, Tachibana A, Hirose J, Yomoda J, Morimoto S, Kuramoto T, Voigt B, Watanabe T, Hiai H, Tateno C, Komatsu K, Serikawa T.
  • Journal Title: Cell Reports Volume: 2(3) Issue: 3 Pages: 685-694
  • DOI: 10.1016/j.celrep.2012.08.009
  • Peer Reviewed
• [Journal Article] DNA-PK inhibition causes a low level of H2AX phosphorylation and homologous recombination repair in Medaka (Oryzias latipes) cells. Biochem. (2012)
  • Author(s): Urushihara, Y., Kobayashi, J., Matsumoto, Y., Komatsu, K, Oda, S., Mitani, H.
  • Journal Title: Biophys.Res.Commun. Volume: 429 Issue: 3-4 Pages: 131-136
  • DOI: 10.1016/j.bbrc.2012.10.128
  • Peer Reviewed
• [Presentation] Nucleolin participates in DNA double-strand break-induced damage response through MDC1-dependent pathway. (2013)
  • Author(s): Junya Kobayashi
  • Organizer: 3rd Asian Congress of Radiation Research (ACRR2013)
  • Place of Presentation: 北京（中国）
  • Invited
• [Presentation] The role of cytoplasmic MRE11 and its relationship with ATM. (2013)
  • Author(s): Junya Kobayashi
  • Organizer: 15th International Workshop on Ataxia-Telangiectasia (ATW2013)
  • Place of Presentation: Birmingham (UK)
  • Invited
• [Presentation] NBSl participates in the regulation of translesion DNA synthesis through Radix and WRN. (2012)
  • Author(s): Kobayashi J.
  • Organizer: Gordon Research Conference "Mutagenesis"
  • Place of Presentation: Salve Regina University (Newport市、アメリカ合衆国)
  • Year and Date: 2012-08-21