Molecular mechanisms of DNA damage tolerance for chronic low-dose UV light

• Project/Area Number: 20370002
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Genetics/Genome dynamics
• Research Institution: Osaka University
• Principal Investigator: HISHIDA Takashi Osaka University, 微生物病研究所, 准教授 (60335388)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000); Fiscal Year 2010: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2009: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2008: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
• Keywords: 分子遺伝 / DNA損傷 / 紫外線 / DNA修復 / DNA損傷トレランス / 突然変異 / DNA複制 / DNA相同組換え / DNA複製 / 酵母 / ユビキチン

Research Abstract

Uultraviolet (UV) light in from sunlight, which is a primary significant environmental cause of DNA damage, that, if left unrepaired, can lead to cancer- and other disease-causing mutations. In nature, organisms are exposed to chronic low-dose UV (CLUV) as opposed to the acute high doses common to laboratory experiments. Here we examine the response of yeast cells to CLUV and identify a key role for the RAD6 error-free postreplication repair (RAD6 error-free PRR) pathway in promoting cell growth and survival. Notably, we showed that the error-free PRR pathway is specifically important during chronic low-dose UV exposure to prevent counter-productive DNA checkpoint activation and allow cells to proliferate normally. Furthermore, we also showed that suppression of homologous recombination (HR) in PRR-deficient cells by Srs2 is required for checkpoint activation and checkpoint maintenance during CLUV irradiation.

Research Products

• [Journal Article] Srs2 controls DNA damage checkpoint responses via two distinct homologous recombination functions in Saccharomyces cerevisiae. (2010)
  • Author(s): Hishida T., Hirade, Y., Haruta, N., Kubota, Y., Iwasaki, H.
  • Journal Title: Mol.Cell.Biol. 20 Pages: 4840-4850
  • Peer Reviewed
• [Journal Article] Srs2 controls DNA damage checkpoint responses via two distinct homologous recombination functions in Saccharomyces cerevisiae. (2010)
  • Author(s): Hishida T., et al.
  • Journal Title: Mol.Cell.Biol. Volume: 20 Pages: 4840-4850
  • Peer Reviewed
• [Journal Article] RAD6-RAD18-RAD5 pathway-dependent tolerance to chronic low-dose UV light. (2009)
  • Author(s): Hishida T., Kubota, Y., Carr, A. M., Iwasaki, H.
  • Journal Title: Nature 457 Pages: 612-615
  • Peer Reviewed
• [Journal Article] 環境レベルの紫外線に対する生物の耐性獲得戦略 (2009)
  • Author(s): 菱田卓
  • Journal Title: 実験医学(羊土社) 27巻 No.11
• [Journal Article] RAD6-RAD18-RAD5 pathway-dependent tolerance to chronic low-dose UV light. (2009)
  • Author(s): Hishida, T., et al..
  • Journal Title: Hishida, T., et al.. 457 Pages: 612-615
  • Peer Reviewed
• [Journal Article] PCNA mono-ubiquitination and activation of translesion DNA polymerases by DNA polymerase alpha (2009)
  • Author(s): Suzuki, M, et al.
  • Journal Title: J.Biochem. 146 Pages: 13-21
  • Peer Reviewed
• [Journal Article] RAD6-RAD18-RAD5 pathway-dependent tolerance to chronic low-dose UV light. (2009)
  • Author(s): Hishida, T., et al. .
  • Journal Title: Nature 457 Pages: 612-615
  • Peer Reviewed
• [Journal Article] A SUMO-like domain protein, Esc2, is required for genome integrity and sister chromatid cohesion in Saccharomyces cerevisiae. (2008)
  • Author(s): Ohya T., Arai, H., Kubota, Y., Shinagawa, H., Hishida T.
  • Journal Title: Genetics 180 Pages: 41-50
  • Peer Reviewed
• [Journal Article] Essential and distinct roles of the F-box and helicase domains of Fbh1 in DNA damage repair. (2008)
  • Author(s): Sakaguchi, C., Morishita, T., Shinagawa, H., Hishida T.
  • Journal Title: BMC Mol.Biol.9 27
  • Peer Reviewed
• [Journal Article] Essential and distinct roles of the F-box and helicase domainsof Fbhl in DNA damage repair. (2008)
  • Author(s): Sakaguchi, C., et al.
  • Journal Title: BMC Mol. Biol. 9
  • Peer Reviewed
• [Journal Article] A SUMO-like domain protein, Esc2, is required for genome integrity and sister chromatid cohesion in Saccharomyces cerevisiae (2008)
  • Author(s): Ohya, T., et al.
  • Journal Title: Genetics 180 Pages: 41-50
  • Peer Reviewed
• [Presentation] 環境レベルの紫外線照射による突然変異の分子メカニズム (2010)
  • Author(s): 菱田卓
  • Organizer: 第33回日本分子生物学会ワークショップ
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-11
• [Presentation] 環境レベルの紫外線照射による突然変異の分子メカニズム (2010)
  • Author(s): 春田奈美
  • Organizer: 第33回に本分子生物学会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-11
• [Presentation] Roles of TLS polymerases in CLUV-induced mutagenesis in NER-deficient cells, 3R symposium (2010)
  • Author(s): 菱田卓
  • Organizer: Toyama
  • Year and Date: 2010-10-28
• [Presentation] Roles of TLS polymerases in CLUV-induced mutagenesis in NER-deficient cells (2010)
  • Author(s): 春田奈美
  • Organizer: 3R Symposium
  • Place of Presentation: 富山
  • Year and Date: 2010-10-28
• [Presentation] 慢性的な低紫外線照射(CLUV)による突然変異誘導のメカニズム (2010)
  • Author(s): 春田奈美
  • Organizer: 第82回日本遺伝学会
  • Place of Presentation: 札幌
  • Year and Date: 2010-09-22
• [Presentation] DNA二重鎖切断修復に関与するSMC様蛋白質RecNの動態解析 (2010)
  • Author(s): 菱田卓
  • Organizer: 第7回21世紀大腸菌研究会
  • Place of Presentation: 阿蘇(熊本)
  • Year and Date: 2010-06-03
• [Presentation] 相同組換えタンパクSrs2 によるDNA 損傷応答システムの制御メカニズム (2009)
  • Author(s): 菱田卓
  • Organizer: 第32回日本分子生物学会ワークショップ
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-11
• [Presentation] 相同組換えタンパクSrs2によるDNA損傷応答システムの制御機構 (2009)
  • Author(s): 菱田卓
  • Organizer: 日本分子生物学会・ワークショップ
  • Place of Presentation: 横浜(神奈川県)
  • Year and Date: 2009-12-11
• [Presentation] 出芽酵母Esc2のSUMO様ドメインの機能解析 (2009)
  • Author(s): 菱田卓
  • Organizer: SUMO研究会
  • Place of Presentation: 三田(兵庫県)
  • Year and Date: 2009-11-21
• [Presentation] DNA二重鎖切断修復に関与するRecNの動態解析 (2009)
  • Author(s): 菱田卓
  • Organizer: 複製・組換え・修復ワークショップ
  • Place of Presentation: 彦根(滋賀県)
  • Year and Date: 2009-11-02
• [Presentation] 環境レベルの紫外線損傷に対するDNA 損傷トレランスの役割 (2009)
  • Author(s): 菱田卓
  • Organizer: 第81回日本遺伝学会、ワークショップ
  • Place of Presentation: 松本
  • Year and Date: 2009-09-18
• [Presentation] 環境レベルの紫外線損傷に対するDNA損傷トレランスの役割 (2009)
  • Author(s): 菱田卓
  • Organizer: 日本遺伝学会・ワークショップ
  • Place of Presentation: 松本(長野県)
  • Year and Date: 2009-09-17
• [Presentation] DNA二重鎖切断に関与するRecNの動態解析 (2009)
  • Author(s): 菱田卓
  • Organizer: 大腸菌研究会
  • Place of Presentation: 熱海(静岡県)
  • Year and Date: 2009-06-11
• [Presentation] 環境レベルの紫外線損傷に対する細胞の耐性機構 (2009)
  • Author(s): 菱田 卓
  • Organizer: 染色体ワークショップ
  • Place of Presentation: 姫路(兵庫県)
  • Year and Date: 2009-01-26
• [Presentation] The yeast RAD6 pathway-dependent tolerance to chronic low-doseUV light (2008)
  • Author(s): 菱田 卓
  • Organizer: The 6^<th> 3R symposium
  • Place of Presentation: 嬬恋(静岡県)
  • Year and Date: 2008-10-30
• [Presentation] CLUV損傷に対する細胞応答機構 (2008)
  • Author(s): 菱田 卓
  • Organizer: ユビキチン研究会
  • Place of Presentation: 三島(静岡県)
  • Year and Date: 2008-10-06
• [Presentation] The RAD6 post replication repair pathway plays a central role in the response to chronic low dose UV exposure (2008)
  • Author(s): 菱田卓
  • Organizer: Yeast genetics & Molecular biology meeting
  • Place of Presentation: Tronto, Canada
  • Year and Date: 2008-07-26
• [Presentation] Tolerance mechanism to chronic low-dose UV light in yeast (2008)
  • Author(s): 菱田 卓
  • Organizer: Yeat genetics and molecular biology meeting
  • Place of Presentation: トロント(カナダ)
  • Year and Date: 2008-07-26
• [Presentation] The yeast RAD6 pathway suppresses counter productive DNA damage checkpoint activation (2008)
  • Author(s): 菱田 卓
  • Organizer: International symposium on Chromosome Dynamics
  • Place of Presentation: 伊勢(三重県)
  • Year and Date: 2008-05-28
• [Book] 蛋白質核酸酵素(「DNA 複製阻害を回避するDNA損傷トレランス機構」)Vol.54, No.4 (2009)
  • Author(s): 菱田卓
  • Publisher: 共立出版
• [Book] 実験医学 (2009)
  • Author(s): 菱田卓
  • Total Pages: 4
  • Publisher: 羊土社
• [Book] 染色体サイクル「蛋白質核酸酵素増刊号」 (2009)
  • Author(s): 菱田卓
  • Total Pages: 6
  • Publisher: 共立出版
• [Book] 蛋白質核酸酵素 (2009)
  • Author(s): 菱田 卓
  • Publisher: 共立出版(in press)
• [Book] 生化学 (2008)
  • Author(s): 菱田 卓
  • Total Pages: 3
  • Publisher: 日本生化学学会