Physiological role of protein-protein interaction among translesion DNA polymerases in cellular resistance to ultraviolet light

• Project/Area Number: 22510063
• 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: Gakushuin University
• Principal Investigator: YOKOI Masayuki 学習院大学, 理学部生命科学科, 助教 (00322701)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: DNAポリメラーゼ / DNA損傷 / 損傷乗り越え複製 / 紫外線 / polη / 突然変異 / 損傷乗り起え複製

Research Abstract

DNA polymerase η (Polη), whose gene mutation is responsible for the inherited disorder xeroderma pigmentosum variant (XP-V), carries out accurate and efficient TLS against cyclobutane pyrimidine dimer (CPD). Since Polη interacts with Polι and REV1, it is suggested that Polη plays a role in recruitment of these TLS polymerases at lesion site. But it is unclear whether UV sensitivity of XP-V patients is caused not only by defect of Polη activity but also by dysfunction of network between Polη and other TLS polymerases. Here, we examined whether the TLS polymerase network via Polη is important for replicative bypass of CPDs and DNA damage tolerance induced by UV in mouse cells. We observed that UV sensitivity of Polη-deficient mouse cells was moderately rescued by the expression of inactive Polη. Moreover, this recovery of cellular UV sensitivity was mediated by the interaction between Polη and REV1. However, expression of inactive mutant Polη was not able to suppress the striking incidence of UV-induced mutation observed in Polη-deficient cells. Finally we demonstrated that REV1 and Polκ are involved in mutagenic DNA damage tolerance via Polη-REV1 interaction when Polη was failed to bypass its cognate substrates.

Research Products

• [Journal Article] Stalled Polη at its cognate substrate initiates an alternative translesion synthesis pathway via interaction with REV1 (2012)
  • Author(s): Ito, W*., Yokoi, M*., Sakayoshi, N., Sakurai, Y., Akagi, J., Mitani, H., and Hanaoka, F. (*: equal contribution)
  • Journal Title: Genes to Cells Volume: 17 Pages: 98-108
  • Peer Reviewed
• [Journal Article] Identification of new scavengers for hydroxyl radicals and superoxide dismutase by utilizing ultraviolet A photoreaction of 8-methoxypsoralen and a variety of mutants of Escherichia coli: implications on certain diseases of DNA repair deficiency (2012)
  • Author(s): Ahmad, S.I., Yokoi, M., Hanaoka, F
  • Journal Title: J. Photochem. Photobiol. B Volume: 116 Pages: 30-36
  • Peer Reviewed
• [Journal Article] Identification of new scavengers for hydroxyl radicals and superoxide dismutase by utilizing ultraviolet A photoreaction of 8-methoxypsoralen and a variety of mutants of Escherichia coli: implications on certain diseases of DNA repair deficiency. (2012)
  • Author(s): Ahmad, S.I., Yokoi, M., Hanaoka, F.
  • Journal Title: J. Photochem. Photobiol. B Volume: 116 Pages: 30-36
  • DOI: 10.1016/j.jphotobiol.2012.07.004
  • Peer Reviewed
• [Journal Article] 立体構造から見えてきた損傷乗り越え DNA 複製の分子メカニズム (2011)
  • Author(s): 道津貫太郎、横井雅幸、花岡文雄
  • Journal Title: 放射線生物研究 Pages: 1-14
• [Journal Article] 立体構造から見えてきた損傷乗り越えDNA複製の分子メカニズム (2011)
  • Author(s): 道津貫太郎、横井雅幸、花岡文雄
  • Journal Title: 放射線生物研究 Volume: 46 Pages: 1-14
• [Presentation] Rev1-dependent activity of Polκcontributes to translesion synthesis past UV-induced DNA lesions (2012)
  • Author(s): Suzuki, K., Akagi, J., Ohashi, E., Yokoi, M., Ohmori,H., and Hanaoka, F
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-12
• [Presentation] Establishment of mouse expressing inactive DNA polymerase η (2012)
  • Author(s): Morita, D., Sakurai, Y., Sakayoshi, N., Ito, W., Yokoi, M., Hanaoka, F
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-12
• [Presentation] Alternative translesion synthesis pathway via interaction between stalled DNA polymerase η and REV1 (2012)
  • Author(s): Hanaoka, F., Yokoi, M
  • Organizer: 第8回 3R Symposium
  • Place of Presentation: 淡路夢舞台
  • Year and Date: 2012-11-27
• [Presentation] Physiological role of DNA polymerase ι in suppression of UV-induced mutagenesis (2012)
  • Author(s): Yokoi, M., Ito, W., Otomo,M., and Hanaoka, F
  • Organizer: 第8回 3R Symposium
  • Place of Presentation: 淡路夢舞台
  • Year and Date: 2012-11-27
• [Presentation] Functional roles of mammalian DNA polymerase η, the product of the XP-V responsible gene (2012)
  • Author(s): Hanaoka, F., Yokoi, M
  • Organizer: 3rdErling Seeberg Symposium
  • Place of Presentation: Trondheim and Orland, Norway
  • Year and Date: 2012-06-21
• [Presentation] ηPhysiological role of DNA polymerase η-REV1 interaction in mammalian cells (2012)
  • Author(s): Yokoi, M., and Hanaoka, F
  • Organizer: Cantoblanco Workshops
  • Place of Presentation: Madrid, Spain
  • Year and Date: 2012-06-06
• [Presentation] Involvement of DNA polymerase η-REV1 interaction in a part of error-prone translesion DNA synthesis (2012)
  • Author(s): Hanaoka, F., Yokoi, M
  • Organizer: US-Japan DNA Repair Workshop
  • Place of Presentation: Leesburg, USA
  • Year and Date: 2012-04-13
• [Presentation] Physiological role of DNA polymerase η-REV1 interaction in mammalian cells. (2012)
  • Author(s): Yokoi, M,, Hanaoka, F.
  • Organizer: Cantoblanco Workshops
  • Place of Presentation: Madrid, Spain
  • Invited
• [Presentation] Physiological role of DNA polymerase ι in suppression of UV-induced mutagenesis. (2012)
  • Author(s): Yokoi, M., Ito, W., Otomo, M., Hanaoka, F.
  • Organizer: 第8回 3R Symposium
  • Place of Presentation: 兵庫県立淡路夢舞台国際会議場
• [Presentation] An alternative TLS pathway for UV-induced DNA damages induced by Polη-REV1 interaction (2011)
  • Author(s): Yokoi, M., Ito, W., Hanaoka, F.
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜(招待講演)
  • Year and Date: 2011-12-15
• [Presentation] An alternative TLS pathway for UV-induced DNA damages induced by Polη-REV1 interaction (2011)
  • Author(s): Yokoi, M., Ito, W., and Hanaoka, F
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-14
• [Presentation] Polκ contributes to suppression of UV-induced mutagenesis (2011)
  • Author(s): Suzuki, K., Akagi, J., Ohashi, E., Yokoi, M., Ohmori.H., and Hanaoka, F
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-14
• [Presentation] Unidentified function of DNA polymerase η and ι in cellular sensitivity to an oxidizing agent potassium bromate (2011)
  • Author(s): Dotsu, K., Sakurai, Y., Ohkumo, T., Yokoi, M., and Hanaoka, F
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-14
• [Presentation] Stalled polη at its cognate substrate emerged an alternative TLS pathway via interaction with REV1 (2011)
  • Author(s): Ito, W., Yokoi, M., Mitani, H., Ohmori,H., Hanaoka, F
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-14
• [Presentation] Tissue-specific roles of DNA polymerase η and ι in UV-induced mutagenesis and DNA damage tolerance (2011)
  • Author(s): Sakurai, Y., Yokoi, M., Ohkumo, T., Hanaoka, F
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-14
• [Presentation] Roles of DNA polymerase η and ι in translesion synthesis past UVB-induced DNA lesions: division of labor at mouse skin (2011)
  • Author(s): Yokoi, M., Sakurai, Y., and Hanaoka, F
  • Organizer: Responses to DNA Damage: From MolecularMechanism to Human Disease
  • Place of Presentation: The Netherlands
  • Year and Date: 2011-04-05
• [Presentation] Roles of DNA polymerase η and ι in translesion synthesis past UVB-induced DNA lesions : division of labor at mouse skin (2011)
  • Author(s): Yokoi, M., Sakurai, Y., Hanaoka, F.
  • Organizer: Responses to DNA Damage : From Molecular Mechanism to Human Disease
  • Place of Presentation: Egmond aan Zee, The Netherlands
  • Year and Date: 2011-04-05
• [Presentation] Analysis of back-up mechanism in translesion synthesis past CPD in the absence of Polη activity (2010)
  • Author(s): Ito, W., Yokoi, M., Mitani, H., Hanaoka, F
  • Organizer: BMB2010
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-08
• [Presentation] Unidentified function of DNA polymeraseη and ι in cellular sensitivity to potassium bromate (2010)
  • Author(s): Dotsu, K., Sakurai, Y., Ohkumo, T., Yokoi, M., Hanaoka, F
  • Organizer: BMB2010
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-08
• [Presentation] Roles of DNA polymeraseη and ι in UV-induced mutagenesis and DNA damage tolerance (2010)
  • Author(s): Sakurai, Y., Yokoi, M., Ohkumo, T., Tsukamoto, T., Tatematsu, M., Wei, M., Wanibuchi, H., Hanaoka, F
  • Organizer: BMB2010
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-08
• [Presentation] Tissue specific function of DNA polymerases η and ι in suppression of UV-induced skin tumor and mutagenesis (2010)
  • Author(s): Yokoi, M., Sakurai, Y., and Hanaoka, F
  • Organizer: The 7th3R Symposium
  • Place of Presentation: 富山カンファレンスセンター(富山県)
  • Year and Date: 2010-10-26
• [Presentation] Tissue specific function of DNA polymerases η and ι in suppression of UV-induced skin tumor and mutagenesis (2010)
  • Author(s): 禎井雅幸
  • Organizer: The 7^<th> 3R Symposium
  • Place of Presentation: 富山カンファレンスセンター(富山県)
  • Year and Date: 2010-10-26
• [Presentation] UV照射DNAの損傷乗り越え複製におけるDNAポリメラーゼイータとイオタの生体内での役割 (2010)
  • Author(s): Sakurai, Y., Yokoi, M., Tsukamoto, T., Tatematsu, M., Wei, M., Wanibuchi, H., Hanaoka, F
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-24
• [Presentation] ノックアウトマウスを用いた紫外線損傷乗り越え複製の解析 (2010)
  • Author(s): 横井雅幸
  • Organizer: 平成22年度 京都大学原子炉実験所専門研究会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-11
• [Presentation] Roles of DNA polymerase η and ι in translesion synthesis past UVB-induced DNA lesions in vivoGordon Research Conference (2010)
  • Author(s): Yokoi, M., Sakurai, Y., Tsukamoto, T., Tatematsu, M., Hanaoka, F
  • Organizer: Mutagenesis
  • Place of Presentation: Waterville, USA
  • Year and Date: 2010-08-04
• [Presentation] UVB照射DNAの損傷乗り越え複製におけるDNAポリメラーゼηとιの生体内での役割 (2010)
  • Author(s): 櫻井靖高、横井雅幸、大雲剛志、道津貫太郎、塚本徹哉、立松正衛、花岡文雄
  • Organizer: 第62回日本細胞生物学会大会
  • Place of Presentation: 大阪
  • Year and Date: 2010-05-19
• [Presentation] CPDの損傷乗り越え複製におけるDNAポリメラーゼηとREV1との相互作用の役割 (2010)
  • Author(s): 伊藤若菜、横井雅幸、坂吉伸隆、星本英史、三谷啓志、花岡文雄
  • Organizer: 第62回日本細胞生物学会大会
  • Place of Presentation: 大阪
• [Remarks] 学習院大学理学部 花岡研究室(分生生物学)
  • URL: http://www-cc.gakushuin.ac.jp/~20080213/
• [Remarks] 学習院大学理学部 花岡研究室（分子生物学）
  • URL: http://www-cc.gakushuin.ac.jp/~20080213/
• [Remarks]
  • URL: http://www-cc.gakushuin.ac.jp/~20080213/
• [Remarks]
  • URL: http://www-cc.gakushuin.ac.jp/~20080213/