Role of nucleolus and related proteins for genomic stability

• Project/Area Number: 21310035
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• 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): HAYASHI Ikue 広島大学, 医歯薬学総合研究科, 助教 (00346503)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2011: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2010: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2009: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
• Keywords: 核小体 / nucleolin / DNA損傷 / チェックポイント / DNA修復

Research Abstract

This study was carried out to clarify the roles of nucleolus, which contains multi-copy of ribosomal DNA and forms specific structure compared with other genomic DNA regions, and nucleolus-related protein for genomic stability. As a result, we found that a major nucleolar protein, nucleolin could function for DNA repair and cell cycle checkpoint following irradiation. Furthermore, nucleolus-localizing protein, WRN and its interaction with NBS1 and Rad18/PCNA could participate in the regulation of trans-lesion DNA synthesis. Therefore, nucleolus-related proteins might be important for maintenance of genomic stability against various genomic stresses.

Research Products

• [Journal Article] NBS1 recruits RAD18 via aRAD6-like domain and regulates Polη-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 CM, Mori T, Zou L, Komatsu K.
  • Journal Title: Mol Cell Volume: 43 Issue: 5 Pages: 788-797
  • DOI: 10.1016/j.molcel.2011.07.026
  • Peer Reviewed
• [Journal Article] Regulation of homologous recombination by RNF20-dependent H2Bubiquitination (2011)
  • Author(s): Nakamura K, Kato A, Kobayashi J, Yanagihara H, Sakamoto S, Oliveira D, Shimada S, Tauchi H, Suzuki H, Tashiro S, Zou L, Komatsu K.
  • Journal Title: Mol Cell Volume: 41 Issue: 5 Pages: 515-528
  • DOI: 10.1016/j.molcel.2011.02.002
  • NAID: 130007000484
  • Peer Reviewed
• [Journal Article] Proteome analysis of proteins related to aggressive periodontitis combined withneutrophil chemo taxis dysfunction (2011)
  • Author(s): Mizuno N, Niitani M, Shiba H, Iwata T, Hayashi I, Kawaguchi H, Kurihara H.
  • Journal Title: J Clin Periodontol Volume: 38 Issue: 4 Pages: 310-7
  • DOI: 10.1111/j.1600-051x.2010.01693.x
  • Peer Reviewed
• [Journal Article] Possible role of WRN protein in cellular response induced by a little DNA damage (2011)
  • Author(s): Kobayashi J, 4名中1番, 他3名
  • Journal Title: Fusion Sicence and Technology Volume: 60 Pages: 1186-1189
  • Peer Reviewed
• [Journal Article] Bisbenzamidine derivative, pentamidine represses DNA damage response through inhibition of his tone H2Aacetylation (2010)
  • Author(s): Kobayashi J, Kato A, Ota Y, Ohba R, Komatsu K.
  • Journal Title: Mol. Cancer Volume: 9 Issue: 1 Pages: 34-34
  • DOI: 10.1186/1476-4598-9-34
  • Peer Reviewed
• [Journal Article] WRN participates intranslesion synthesis pathway through interaction with NBS1 (2010)
  • Author(s): Kobayashi J, Okui M, Asaithamby A, Burma S, Chen BP, Tanimoto K, MatsuuraS, Komatsu K, Chen DJ.
  • Journal Title: Mech Ageing Dev Volume: 131 Issue: 6 Pages: 436-444
  • DOI: 10.1016/j.mad.2010.06.005
  • Peer Reviewed
• [Journal Article] Acquiredradioresistance of human tumor cells byDNA-PK/AKT/GSK3beta-mediated cyclin D1overexpression (2010)
  • Author(s): Shimura T, Kakuda S, Ochiai Y, NakagawaH, Kuwahara Y, Takai Y, Kobayashi J, Komatsu K, Fukumoto M.
  • Journal Title: Oncogene Volume: 29 Issue: 34 Pages: 4826-4837
  • DOI: 10.1038/onc.2010.238
  • Peer Reviewed
• [Journal Article] Bisbenzamidine derivative, pentamidine represses DNA damage response through inhibition of histone H2A acetylation. (2010)
  • Author(s): Kobayashi J, (5名中1番), 他4名
  • Journal Title: Molecular Cancer Volume: 9(論文番号) Pages: 34-34
  • NAID: 120002515185
  • Peer Reviewed
• [Journal Article] WRN participates in translesion synthesis pathway through interaction with NBS1. (2010)
  • Author(s): Kobayashi J, (9名中1番), 他8名
  • Journal Title: Mech.Ageing Dev. Volume: 131 Pages: 436-444
  • NAID: 120002426896
  • Peer Reviewed
• [Journal Article] Acquired radioresistance of human tumor cells by DNA-PK/AKT/GSK3beta-mediated cyclin D1 overexpression. (2010)
  • Author(s): Shimura T, Kobayashi J, (9名中7番)
  • Journal Title: Oncogene Volume: 29 Pages: 4826-4837
  • Peer Reviewed
• [Journal Article] His tone H2AX participates the DNA damage-induced ATM activation throughinteraction with NBS1 (2009)
  • Author(s): Kobayashi J, Tauchi H, Chen B, Bruma S, Tashiro S, Matsuura S, Tanimoto K, Chen DJ, Komatsu K.
  • Journal Title: Biochem Biophys Res Commun Volume: 380 Issue: 4 Pages: 752-757
  • DOI: 10.1016/j.bbrc.2009.01.109
  • Peer Reviewed
• [Journal Article] Inactivation of the Nijmegen breakage syndrome gene NBS1 leads to excess centrosome duplication via the ATR/BRCA1 pathway (2009)
  • Author(s): Shimada M, Sagae R, Kobayashi J, Habu T, Komatsu K.
  • Journal Title: Cancer Research Volume: 69 Issue: 5 Pages: 1768-1775
  • DOI: 10.1158/0008-5472.can-08-3016
  • Peer Reviewed
• [Journal Article] Histone H2AX participates the DNA damage-induced ATM activation through interaction with NBS1 (2009)
  • Author(s): Kobayashi J, (9名中1番), 他8名
  • Journal Title: Biochem Biophys Res Commun. 380 Pages: 752-757
  • Peer Reviewed
• [Journal Article] DNA double-strand break formation upon UV-induced replication stress activates ATM and DNA-PKcs kinases (2009)
  • Author(s): Yajima H, Kobayashi J, (5名中4番)
  • Journal Title: J Mol Biol. 385 Pages: 800-810
  • Peer Reviewed
• [Journal Article] Inactivation of the Nijmegen breakage syndrome gene NBS1 leads to excess centrosome duplication via the ATR/BRCA1 pathway (2009)
  • Author(s): Shimada M, Kobayashi J, (5名中3番)
  • Journal Title: Cancer Research 69 Pages: 1768-1775
  • Peer Reviewed
• [Presentation] Novel role ofNBS1 in ubiquitination-mediated response through RNF20 (2012)
  • Author(s): Kobayashi J(小林純也)他
  • Organizer: 14th International Workshop on Ataxia-Telangiectasia 2012
  • Place of Presentation: New Delhi(India)
  • Year and Date: 2012-02-11
• [Presentation] Novel role of NBS1 in ubiquitination-mediated response through RNF20 (2012)
  • Author(s): Kobayashi J, 5名中1番, 他1名
  • Organizer: The International Workshop on Ataxia-Telangiectasia
  • Place of Presentation: New Delhi (India)
  • Year and Date: 2012-02-11
• [Presentation] Nucleoli participates in MDC1-related DNA damage response (2011)
  • Author(s): Kobayashi J(小林純也)他
  • Organizer: 14th International Congress of Radiation Research
  • Place of Presentation: Warsaw(Poland)
  • Year and Date: 2011-08-30
• [Presentation] 新規H2AX結合因子nucleolinによるATM依存性DNA損傷応答の制御BMB2010 (2010)
  • Author(s): 小林純也, 他
  • Organizer: 日本生化学会・日本分子生物学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-08
• [Presentation] クロマチン修飾を介した放射線誘導DNA損傷応答の制御 (2010)
  • Author(s): 小林純也, 他
  • Organizer: 日本放射線影響学会第53回大会
  • Place of Presentation: 京都
  • Year and Date: 2010-10-20
• [Presentation] The role of novel H2AX-binding factor, nucleolin in ATM-dependent DNA damage response (2010)
  • Author(s): Kobayashi J(小林純也)他
  • Organizer: The International Ataxia-Telangiectasia Workshop 2010
  • Place of Presentation: Los Angels(USA)
  • Year and Date: 2010-04-13
• [Presentation] The role of novel H2AX-binding factor, nucleolin in ATM-dependent DNA damage response. (2010)
  • Author(s): Kobayashi J, (4名中1番), 他3名
  • Organizer: The International Workshop on Ataxia-Telangiectasia
  • Place of Presentation: Los Angeles (USA)(招待講演)
  • Year and Date: 2010-04-13
• [Presentation] WRN functions in S phase-dependent DNA damage response through the interaction with NBS1 (2009)
  • Author(s): Kobayashi J(小林純也)他
  • Organizer: 2nd Asian Congress of Radiation Research
  • Place of Presentation: Seoul(Korea)
  • Year and Date: 2009-05-18
• [Presentation] WRN functions in S phase-dependent DNA damage response through the interaction with NBS1 (2009)
  • Author(s): Junya Kobayashi
  • Organizer: 2nd Asian Congress of Radiation Research
  • Place of Presentation: Seoul (Korea)
  • Year and Date: 2009-05-18
• [Book] Etiology and Pathogenesis of Periodontal Disease (2010)
  • Author(s): Dumitrescu AL, Kobayashi J, (9名中3番)
  • Total Pages: 323
  • Publisher: Springer (Berline)
• [Book] Genetic Variants in Periodontal Health and Disease (2009)
  • Author(s): Dumitrescu AL, Kobayashi J
  • Total Pages: 135
  • Publisher: Springer(Berlin)
• [Book] Genetic Variants in Periodontal Health and Disease (2009)
  • Author(s): Dumitrescu AL, Kobayashi J.
  • Total Pages: 135
  • Publisher: Springer (Berline)