Analysis of Molecular Mechanism for Regulating Initiation of Recombination-mediated Mitochondrial DNA Replication

• Project/Area Number: 20570171
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Molecular biology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: LING Feng The Institute of Physical and Chemical Research, 吉田化学遺伝学研究室, 専任研究員 (70281665)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 遺伝学 / 遺伝子 / 核酸 / ストレス / 酵素 / DNAの組換え / ミトコンドリア / Saccharomyces cerevisiae / Saccharomvces cerevisias / 組換え / 相同DNA対合 / 除去修復 / ローリングサークル型複製 / 酸化ストレス応答 / DNA複製

Research Abstract

The mechanism for initiation of recombination-mediated mitochondrial DNA (mtDNA) replication is still unclear in budding yeast. We revealed that the oxidative DNA damage-excision repair enzyme Ntg1 recognizes the exposed single-strand region at the sites of oxidative modifications and introduces DNA double-stranded breaks at a replication origin. In addition, the 5'-3' exonuclease and DNA helicases play roles in mtDNA replication-mediated by Mhr1, which in vitro prefers relaxed closed circular double-stranded DNA for catalyzing homologous DNA pairing.

Research Products

• [Journal Article] Gene conversion through double-strand break-induced DNA replication and mitochondrial homoplasmy (2011)
  • Author(s): Feng Ling, Tsutomu Mikawa, Takehiko Shibata
  • Journal Title: Genes 2 Pages: 169-190
  • Peer Reviewed
• [Journal Article] Mitochondrial fusion increases mitochondrial DNA copy number in budding yeast (2011)
  • Author(s): Akiko Hori
  • Journal Title: Genes to Cells Volume: 16(In press)
  • Peer Reviewed
• [Journal Article] Enlightenment of yeast mitochondrial homoplasmy : diversified roles of gene conversion (2011)
  • Author(s): Feng Ling
  • Journal Title: Genes Volume: 2 Pages: 169-190
  • Peer Reviewed
• [Journal Article] Analysis of DNA-binding sites on Mhr1, a yeast mitochondrial ATP-independent homologous pairing protein (2010)
  • Author(s): Tokiha Masuda, Feng Ling, Takehiko Shibata, Tsutomu Mikawa
  • Journal Title: FEBS Journal 277 Pages: 1440-1452
  • Peer Reviewed
• [Journal Article] Analysis of DNA-binding sites on Mhr1, a yeast mitochondrial ATP-independent homologous pairing protein (2010)
  • Author(s): Tokiha Masuda
  • Journal Title: FEBS Journal Volume: 277 Pages: 1440-1452
  • Peer Reviewed
• [Journal Article] Analysis of DNA-binding sites on Mhr1, a yeast mitochondrial ATP-independent homologous pairing protein (2010)
  • Author(s): Tokiha Masuda
  • Journal Title: FEBS Journal 277 Pages: 1440-1452
  • Peer Reviewed
• [Journal Article] Negative supercoil interference with homologous pairing mediated by Mhr1, an ATP-independent recombinase structurally unrelated to RecA/Rad51 (2009)
  • Author(s): Feng Ling, Minoru Yoshida, Takehiko Shibata
  • Journal Title: The Journal of Biological Chemistry 284 Pages: 9341-9353
  • Peer Reviewed
• [Journal Article] Reactive oxygen species contribute to recombination-mediated replication to regulate the mitochondrial DNA copy number (2009)
  • Author(s): Akiko Hori, Minoru Yoshida, Takehiko Shibata, Feng Ling
  • Journal Title: Nucleic Acids Research 37 Pages: 749-761
  • Peer Reviewed
• [Journal Article] Heteroduplex joint formation free of net topological change by Mhr1, a mitochondrial recombinase (2009)
  • Author(s): Feng Ling
  • Journal Title: The Journal of Biological Chemistry 284 Pages: 9341-9353
  • Peer Reviewed
• [Journal Article] Reactive oxygen species regulate DNA copy number in isolated yeast mitochondria by triggering recombination-mediated replication (2009)
  • Author(s): Akiko Hori
  • Journal Title: Nucleic Acids Research 37 Pages: 749-761
  • Peer Reviewed
• [Journal Article] Heteroduplex joint formation free of net topological change by Mhr1, a mitochondrial recombinase (2009)
  • Author(s): Feng Ling
  • Journal Title: Journal of Biological Chemistry 284(印刷中)
  • Peer Reviewed
• [Journal Article] Reactive oxygen species regulate DNA copy number in isolated yeast mitochondria by triggering recombination-mediated replication (2009)
  • Author(s): Akiko Hori
  • Journal Title: Nucleic Acids Research
  • Peer Reviewed
• [Journal Article] The yeast checkpoint kinase Dun1 down-regulates DIN7 in the absence of DNA damage (2008)
  • Author(s): Ayako Yoshitani, Feng Ling, Minoru Yoshida
  • Journal Title: Bioscience, Biotechnology, and Biochemistry 72(6) Pages: 1630-1634
  • Peer Reviewed
• [Journal Article] A novel cis-acting element required for DNA damage-inducible expression of yeast DIN7. (2008)
  • Author(s): Ayako Yoshitani, Minoru Yoshida, Feng Ling
  • Journal Title: Biochemical and Biophysical Research Communications 365(1) Pages: 183-188
  • Peer Reviewed
• [Journal Article] The yeast checkpoint kinase Dun1 downregulates DIN7 in the absence of DNA damage (2008)
  • Author(s): Ayako Yoshitani
  • Journal Title: Bioscience, Biotechnology, and Biochemistry 72(6) Pages: 1630-1634
  • Peer Reviewed
• [Journal Article] A novel cis-acting element required for DNA damage-inducible expression of yeast DIN7 (2008)
  • Author(s): Ayako Yoshitani
  • Journal Title: Biochemical and Biophysical Research Communications 365(1) Pages: 183-185
  • Peer Reviewed
• [Presentation] Mitochondrial DNA homoplasmy as gene homogenization of repeated sequences by rolling circle replication. (2011)
  • Author(s): Takehiko Shibata, Feng Ling, Tsutomu Mikawa
  • Organizer: The 7th conference of Asian Societyfor mitochondrial research and Medicine and 10th Japanese Society for mitochondrial research and Medicine
  • Place of Presentation: Fukuoka city
  • Year and Date: 2011-12-16
• [Presentation] Mitochondrial DNA homoplasmy as gene homogenization of repeated sequences by rolling circle replication. (2011)
  • Author(s): Feng Ling, Rong Niu, Elliot Bradshaw, Takehiko Shibata, Minoru Yoshida
  • Organizer: RIKEN Joint Retreat 2011
  • Place of Presentation: Yamaha Resort Tsumagi, Kakegawa, Shizuoka
  • Year and Date: 2011-01-31
• [Presentation] A Molecular Mechanism for Mitochondrial DNA Homoplasmy and its Application (2011)
  • Author(s): Feng Ling
  • Organizer: RIKEN Joint Retreat 2011
  • Place of Presentation: Yamaha Resort Tsumagi, Kakegawa, Shizuoka
  • Year and Date: 2011-01-31
• [Presentation] Mitochondrial DNA homoplasmy as gene homogenization of repeated sequences by rolling circle replication. (2010)
  • Author(s): Takehiko Shibata
  • Organizer: The 7^<th> conference of Asian Societyfor mitochondrial research and Medicine and 10^<th> Japanese Society for mitochondrial research and Medicine
  • Place of Presentation: Fukuoka city
  • Year and Date: 2010-12-16
• [Presentation] ROSで誘導される組換え依存型ミトコンドリアDNA複製 (2009)
  • Author(s): 凌楓、堀晶子,牛栄、柴田武彦、吉田稔
  • Organizer: 第9回日本ミトコンドリア学会年会
  • Place of Presentation: 東京大学医学部鉄門記念講堂
  • Year and Date: 2009-12-17
• [Presentation] ミトコンドリアDNAコピー数を増加させるミトコンドリア融合 (2009)
  • Author(s): 堀晶子、吉田稔、凌楓
  • Organizer: 第32回日本分子生物学年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-12-10
• [Presentation] ROSで誘導される組換え依存型ミトコンドリアDNA複製 (2009)
  • Author(s): 堀晶子
  • Organizer: 第32回日本分子生物学年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-12-10
• [Presentation] 相同DNA組換えにおける天然変性領域の機能 (2009)
  • Author(s): 柴田武彦
  • Organizer: 第82回生化学会大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2009-10-21
• [Presentation] DNAの位相幾何学的変化を伴わない組換え中間体形成 (2009)
  • Author(s): 柴田武彦
  • Organizer: 第26回染色体ワークショップ
  • Place of Presentation: 姫路
• [Presentation] ミトコンドリアの相同組換え酵素反応へのDNAの高次構造の効果 (2008)
  • Author(s): 凌楓、吉田稔、柴田武彦
  • Organizer: 第8回日本ミトコンドリア学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-14
• [Presentation] 酵母ミトコンドリアDNA複製開始点での二重鎖切断修復に働く相同DNA対合酵素Mhr1 (2008)
  • Author(s): 凌楓、堀晶子、柴田武彦、吉田稔
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会(BMB2008)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] DNAの位相幾何学的変化を伴わない組換え中間体形成 (2008)
  • Author(s): 柴田武彦、凌楓
  • Organizer: 第26回染色体ワークショップ
  • Place of Presentation: 姫路
  • Year and Date: 2008-01-16
• [Presentation] ミトコンドリアの相同組換え酵素反応へのDNAの高次構造の効果 (2008)
  • Author(s): 凌楓
  • Organizer: 第8回日本ミトコンドリア学会年会
  • Place of Presentation: 東京
• [Presentation] 出芽酵母のミトコンドリアDNAの複製開始領域に起きる二重鎖切断導入機構 (2008)
  • Author(s): 堀晶子
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会(BMB2008)
  • Place of Presentation: 神戸
• [Presentation] 出芽酵母のミトコンドリアDNAの複製開始領域に起きる二重鎖切断導入機構
  • Author(s): 堀晶子、柴田武彦、吉田稔、凌楓
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会(BMB2008)
• [Remarks] ホームページ等
• [Patent(Industrial Property Rights)] ヘテロプラスミー細胞をホモプラスミー化する方法 (2009)
  • Inventor(s): 凌楓、柴田武彦、牛栄、吉田稔、後藤雄一
  • Industrial Property Rights Holder: 独立行政法人理化学研究所
  • Industrial Property Number: 2009-285729
  • Filing Date: 2009-12-16