Identification and characterization of the roles in mutation prevention of repair enzymes for oxidative base damage in DNA caused by ionizing radiation and reactive oxygen species

2008 Fiscal Year Final Research Report

• Project/Area Number: 19510056
• 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: Kyoto University
• Principal Investigator: AKIYAMA-ZHANG Qiu-mei (張 秋梅) Kyoto University, 大学院・理学研究科, 准教授 (00260604)
• Project Period (FY): 2007 – 2008
• Keywords: 電離放射線 / 活性酸素 / 酸化的塩基損傷 / 塩基除去修復 / 突然変異 / DNAグリコシラーゼ / 線虫 / KsgA

Research Abstract

放射線や活性酸素はDNAに多様な損傷を引き起こす。生じる塩基酸化体, チミングリコール, 5-ホルミルウラシルや8-オキソグアニンは突然変異を誘発する損傷である。生物は, これらの損傷をDNAから除去することで突然変異を抑制する防御システムを備えている。本研究では, 分裂酵母, 線虫, 大腸菌での塩基酸化体をDNAから除去する新規のDNAグリコシラーゼを同定し, それらの酵素が自然および酸化ストレスで誘発される突然変異を抑制することを明らかにした。

Research Products

• [Journal Article] Purification and characterization of Caenorhabditis elegans NTH, a homolog of human endonuclease III : essential role of Nterminal region (2009)
  • Author(s): Morinaga, H., S. Yonekura, N. Nakamura, H. Sugiyama, S. Yonei and Q-M, Zhang-Akiyama
  • Journal Title: DNA Repair (in press)
  • Peer Reviewed
• [Journal Article] KsgA, a 16S rRNA adenine methyltransferase, has a novel DNA glycosylase/AP lyase activity to prevent mutations in Escherichia coli (2009)
  • Author(s): Zhang-Akiyama, Q-M., H. Morinaga, M. Kikuchi, S. Yonekura, H. Sugiyama, K. Yamamoto and S. Yonei
  • Journal Title: Nucleic Acids Res. (in press)
  • Peer Reviewed
• [Journal Article] Yonekura, S., N. Nakamura, S. Yonei and Q-M. Zhang-Akiyama (2009)
  • Author(s): Yonekura, S., N. Nakamura, S. Yonei and Q-M. Zhang-Akiyama
  • Journal Title: J. Radiat. Res. 50 Pages: 19-26
  • Peer Reviewed
• [Journal Article] Human Nei-like protein NEIL3 has AP lyase activity specific for single-stranded DNA and confers oxidative stress resistance in Escherichia coli mutant (2009)
  • Author(s): Takao, M., Y. Oohata, K. Kitadokoro, K. Koba-yashi, S. Iwai, A. Yasui, S. Yonei, Q-M. Zhang
  • Journal Title: Genes to Cells 14 Pages: 261-270
• [Journal Article] (2008)
  • Author(s): Nakamura, N., H. Morinaga, M. Kikuchi, S. Yonekura, N. Ishii, K. Yamamoto, S. Yonei and Q-M. Zhang
  • Journal Title: Mutagenesis 23 Pages: 407-413
  • Peer Reviewed
• [Journal Article] Primary research of human anti-oxidant gene GLRX2 and TXN1 (2008)
  • Author(s): Wang, L.-L. and Q-M. Zhang
  • Journal Title: J. Biol. 25 Pages: 17-20
  • Peer Reviewed
• [Journal Article] Recombinant Schizosaccharomyces pombe Nth1 protein exhibits DNA glycosylase activities for 8-oxo-7.8-dihydroguanine and thymine residues oxidized in the methyl group (2007)
  • Author(s): Yonekura, S., N. Nakamura, T. Doi, H. Sugiyama, K. Yamamoto, S. Yonei and Q-M. Zhang
  • Journal Title: J. Radiat. Res. 48 Pages: 417-424
  • Peer Reviewed
• [Journal Article] Overexpression of DNA polymerase β results in an increased rate of frameshift mutations during base excision repair (2007)
  • Author(s): Chan, K., S. Houlbrook, Q-M. Zhang, M. Harrison, L. D. Hickson and G. L. Dianov
  • Journal Title: Mutagenesis 31 Pages: 1-6
  • Peer Reviewed
• [Journal Article] シトシン脱アミノ化の生物作用とその修復の機構 (2007)
  • Author(s): 中村允耶、米倉慎一郎、森永浩伸、米井脩治、張秋梅
  • Journal Title: 放射線生物研究 42 Pages: 132-146
• [Presentation] 真核生物OXR1タンパク質の機能解析 (2008)
  • Author(s): 橋口一成、浅井翔太、米井脩治、秋山(張)秋梅
  • Organizer: 日本分子生物学会第31回大会-日本生化学会第81回大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 20081209-12
• [Presentation] 線虫C. elegansのNth1ホモログの同定と構造機能の解析 (2008)
  • Author(s): 森永浩伸、米倉慎一郎、米井脩治、石井直明、秋山(張)秋梅
  • Organizer: 日本分子生物学会第31回大会-日本生化学会第81回大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 20081209-12
• [Presentation] The role of the C. elegans OXR1 homolog in protection against oxidative stress (2008)
  • Author(s): S. Asai and Q-M. Zhang-Akiyama
  • Organizer: The 2^<nd> International Symposium of the Biodiversity Global COE Project
  • Place of Presentation: Kyoto
  • Year and Date: 20081121-22
• [Presentation] Identification and characterization of NTH homolog in C. elegans (2008)
  • Author(s): H. Morinaga, N. Nakamura, S-I. Yonekura, H Sugiyama, S. Yonei and Q-M. Zhang-Akiyama
  • Organizer: The 2^<nd> International Symposium of the Biodiversity Global COE Project
  • Place of Presentation: Kyoto
  • Year and Date: 20081121-22
• [Presentation] Correlation of cellular radiosensitivity and radiation responses with the levels of thioredoxin in HeLa cells (2008)
  • Author(s): A. Matsui and Q-M. Zhang-Akiyama
  • Organizer: The 2^<nd> International Symposium of the Biodiversity Global COE Project
  • Place of Presentation: Kyoto
  • Year and Date: 20081121-22
• [Presentation] Modulation of cellular effects of ionizing radiation and reactive oxygen species by overexpression of antioxidant enzymes in human cells (2008)
  • Author(s): A. Hosoki and Q-M. Zhang-Akiyama
  • Organizer: The 2^<nd> International Symposium of the Biodiversity Global COE Project
  • Place of Presentation: Kyoto
  • Year and Date: 20081121-22
• [Presentation] Search for MutT functional homolog in C. elegans (2008)
  • Author(s): Y. Sanada and Q-M. Zhang-Akiyama
  • Organizer: The 2^<nd> International Symposium of the Biodiversity Global COE Project
  • Place of Presentation: Kyoto
  • Year and Date: 20081121-22
• [Presentation] 活性酸素防御酵素の高発現による放射線応答の変動 (2008)
  • Author(s): 秋山(張)秋梅、細木彩夏、松井亜子、橋口一成、野村崇治、近藤隆
  • Organizer: 日本放射線影響学会第51回大会
  • Place of Presentation: 北九州
  • Year and Date: 20081119-21
• [Presentation] 抗酸化酵素の高発現による放射線や活性酸素に対する細胞応答の変動 (2008)
  • Author(s): 細木彩夏、橋口一成、近藤 隆、野村崇治、米井脩治、秋山(張)秋梅
  • Organizer: 日本放射線影響学会第51回大会
  • Place of Presentation: 北九州
  • Year and Date: 20081119-21
• [Presentation] 線虫 C. elegansにおける NTH 遺伝子の同定と解析 (2008)
  • Author(s): 森永浩伸, 米倉慎一郎, 中村允耶, 杉山 弘, 米井脩治, 秋山(張)秋梅
  • Organizer: 日本放射線影響学会第51回大会
  • Place of Presentation: 北九州
  • Year and Date: 20081119-21
• [Presentation] 活性酸素防御酵素の高発現と細胞の放射線応答の変動 (2008)
  • Author(s): 松井亜子、橋口一成、近藤 隆、野村崇治、米井脩治、秋山(張)秋梅
  • Organizer: 日本放射線影響学会第51回大会
  • Place of Presentation: 北九州
  • Year and Date: 20081119-21
• [Presentation] 線虫 C.elegansにおけるウラシルDNAグリコシラーゼCeUng-1の性質と遺伝子欠損の影響 (2008)
  • Author(s): 秋山秋梅、中村允耶、森永浩伸、菊地政弘、石井直明
  • Organizer: 日本遺伝学会第80回大会
  • Place of Presentation: 名古屋
  • Year and Date: 20080903-05
• [Presentation] KsgA, a rRNA methyltransferase, has a novel DNA glycosylase/AP lyase activity that removes cytosine paired with oxidative damage of thymine (2008)
  • Author(s): Q-M. Zhang, Hironobu Morinaga, Shin-Ichiro Yonekura, Naoaki Ishii and Shuji Yonei
  • Organizer: 10th International Workshop Radiation Damage to DNA
  • Place of Presentation: Fukushima
  • Year and Date: 20080608-12
• [Presentation] Comparative Analysis of Structure and Functions of MutT Homologs (2008)
  • Author(s): M. Kikuchi, Shin-Ichiro Yonekura and Q-M. Zhang
  • Organizer: The 1st International Symposium of the Biodiversity Global COE Project
  • Place of Presentation: Kyoto
  • Year and Date: 20080319-20
• [Presentation] Biological Diversity of Oxidative Stress Response (2008)
  • Author(s): Shin-Ichro Yonekura and Q-M. Zhang
  • Organizer: The 1st International Symposium of the Biodiversity Global COE Project
  • Place of Presentation: Kyoto
  • Year and Date: 20080319-20
• [Presentation] スーパーオキサイドによって誘導されるydbK遺伝子のプロモーターと機能 (2007)
  • Author(s): 米倉慎一郎、米井脩治、張秋梅
  • Organizer: 日本分子生物学会第30回大会-日本生化学会第80回大会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 20071211-15
• [Presentation] 線虫(Caenorhabditis elegans)におけるMutTホモログの解析 (2007)
  • Author(s): 菊地政弘、米倉慎一郎、中村允耶、米井脩治、張秋梅
  • Organizer: 日本分子生物学会第30回大会-日本生化学会第80回大会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 20071211-05
• [Presentation] 抗酸化酵素の高発現によるヒト細胞での放射線感受性の変動 (2007)
  • Author(s): 張秋梅, 中島恭子, L-L. Wang, 蓮池史画, 立花章, 野村崇治, 米倉慎一郎, 米井脩治
  • Organizer: 日本放射線影響学会第50回大会
  • Place of Presentation: 千葉
  • Year and Date: 20071114-17
• [Presentation] 線虫Caenorhabditis elegansおよびホヤCiona intestinalisにおけるMutTホモログの同定と解析 (2007)
  • Author(s): 菊地政弘, 米倉慎一郎, 中村允耶, 米井脩治, 張秋梅
  • Organizer: 日本放射線影響学会第50回大会
  • Place of Presentation: 千葉
  • Year and Date: 20071114-17
• [Presentation] スーパーオキサイド誘導性ydbK遺伝子のプロモーターとYdbKタンパク質の抗酸化機能 (2007)
  • Author(s): 米倉慎一郎、米井脩治、張秋梅
  • Organizer: 日本放射線影響学会第50回大会
  • Place of Presentation: 千葉
  • Year and Date: 20071114-17
• [Book] Establishment of human cell lines lacking mitochondrial DNA. In Methods in Molecular Biology. Mitochondria DNA : Methods and Protocols (2009)
  • Author(s): Hashiguchi, K. and Q-M. Zhang-Akiyama
  • Publisher: Humana Press (New Jersey)(in pres)