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A role of Holliday structure in mitochondrial genome maintenance

Research Project

Project/Area Number 13670146
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionKyushu University

Principal Investigator

KANG Dongchon  Kyushu University, Graduate School of Medical Sciences, Department of Clinical Chemistry and Laboratory Medicine, Associate Professor, 医学研究院, 助教授 (80214716)

Co-Investigator(Kenkyū-buntansha) ABE Yoshito  Kyushu University, Department of Clinical Chemistry and Laboratory Medicine, Assistant Professor, 医学研究院, 助手 (60315091)
HAMASAKI Naotaka  Kyushu University, Department of Clinical Chemistry and Laboratory Medicine, Professor, 医学研究院, 教授 (00091265)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2001: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywordsmitochondria / mitochondrial DNA / Holliday structure / DNA replication / TFAM / D-loop / R-loop / nucleoid / D-loop / Holliday構造 / mtTFA / mtSSB / MPP+
Research Abstract

During replication, human mitochondrial DNA (mtDNA) takes on a triple-stranded structure known as a D-loop, which is implicated in replication and transcription. 1-Methyl-4-phenylpyridinium ion (MPP^+), a toxin inducing Parkinsonism, inhibits mtDNA replication possibly by resolving the D-loops. For initiation of mtDNA replication, mitochondria are thought to have another triple-stranded structure, an R-loop. The R-loop, which is resolved by a bacterial junction-specific helicase RecG, is also resolved by MPP^+. Because mitochondrial D-loops are resolved by RecG as well, the D- and R-loops may share a similar branched structure. MPP^+ resolves cruciform DNA in supercoiled DNA. MPP^+ converts a stacked conformation to an extended conformation in a synthetic Holliday junction. This conversion is reversed by 1 mM Mg^<2+>, as is the resolution of the D-loops or cruciform DNA. These observations suggest that the junction structure of mitochondrial D- and R-loops is affected by MPP^+. Mitochondrial transcription factor A (TFAM), a member of the high mobility group proteins, is essential for maintenance of mitochondrial DNA (mtDNA). Most TFAM and mtDNA (both of which are normally soluble) was recovered from the particulate fraction of human placental mitochondria when extracted with the non-ionic detergent Nonidet P-40. mtDNA and TFAM were co-immunoprecipitated by anti-TFAM antibodies. Thus, TFAM and mtDNA are tightly associated with each other, and it is likely that few TFAM or mtDNA molecules exist in an unbound form in mitochondria. Based on a fact that TFAM is abundant enough to wrap mtDNA entirely, these results suggest that human mtDNA is packaged with TFAM.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Alam et al.: "Human mitochondrial DNA is packaged with TFAM"Nucl. Acids Res.. 31. 1640-1645 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takamatsu et al.: "Regulation of mitochondriat D-loops by transcription factor A and single-stranded DNA-binding protein"EMBO Rep.. 3. 451-456 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohsato et al.: "Mammalian mitochondrial endonuclease G: digestion of R-loops"Eur. J. Biochem.. 269. 5675-5770 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iwaasa et al.: "Genomic cloning and promoter analysis of a mouse anion exchanger 3 (AE3) gene"DNA Seq.. 13. 251-255 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagata et al.: "The regulation of DNAse activities in subcellular compartments of activated thymocytes"Immunology. 105. 399-406 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kang et al.: "Maintenance of mitochondrial DNA integrity: repair and degradation"Curr. Genet.. 41. 313-322 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iwasa, M et al.: "D. 1-Methyl-4-phenylpyridinium ion (MPP+), a toxin that can cause Parkinsonism, alter branched structures of DNA"J. Neurochem.. 82. 30-37 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suematsu, N et al.: "Oxidative stress medates tumor necrosis factor-a induced mitochondrial DNA damage anddysfunction in cardiac myocytes"Circulation.. 108. 1418-1423 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okamoto, M et al.: "D. Ditercalinium dhloride, a pro-anticancer drug"Durr. Genet.. (In press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iwaasa,M., Umeda,S., Ohsato,T., Takamatsu,C., Fukuoh,A., Iwasaki,H., Shinagawa,H., Hamasaki,N. and Kang,D.: "1-Methyl-4-phenylpyridinium ion (MPP+), a toxin that can cause Parkinsonism, alter branched structures of DNA"J.Neurochem.. 82. 30-37 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takamatsu,C., Umeda,S., Ohsato,T., Ohno,T., Abe,Y., Fukuoh,A., Shinagawa,H., Hamasaki,N. and Kang,D.: "Regulation of mitochondrial D-loops by transcription factor A and single-stranded DNA-binding protein"EMBO Rep.. 3. 451-456 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagata,T., Kishi,H., Liu,Q.L., Matsuda,T., Imanaka,T., Tsukada,K., Kang,D. and Muraguchi,A.: "The regulation of DNAse activities in subcellular compartments of activated thymocytes"Immunology. 105. 399-406 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iwaasa,M., Tatewaki,H., Ohno,T., Okubo,K., Hamasaki,N. and Kang,D.: "Genomic cloning and promoter analysis of a mouse anion exchanger 3(AE3) gene"DNA Sequence. 13. 251-255 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohsato,T., Ishihara,N., Muta,T., Umeda,S., Ikeda,S., Mihara,K., Hamasaki,N. and Kang,D.: "Mammalian mitochondrial endonuclease G : digestion of R-loops and localization in intermembrane space"Eur.J.Biochem.. 269. 5675-5770 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Alam,I.T., Kanki,T., Muta,T., Ukaji,K., Abe,A., Nakayama,H., Takio,K., Hamasaki,N. and Kang,D.: "Human mitochondrial DNA is packaged with TFAM"Nucl.Acids Res.. 31. 1640-1645 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suematsu,N., Tsutsui,H., Wen,J., Kang,D., Ikeuchi,M., Ide,T., Hayashidani,S., Shiomi,T., Kubota,T., Hamasaki,N. and Takeshita,A.: "Oxidative stress mediates tumor necrosis factor-a induced mitochondrial DNA damage anddysfunction in cardiac myocytes"Circulation. 108. 1418-1423 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okamaoto,M., Ohsato,T., Nakada,K., Isobe,K., Spelbrink,J., Hayashi,J.-I., Hamasaki,N. and Kang,D.: "Ditercalinium chloride, a pro-anticancer drug"Curr.Genet.. (In press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kang et al: "Maintenance of mitochondrial DNA integrity : repair and degradation"Durr.Genet.. 41. 313-322 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Alam et al.: "Human mitochondrial DNA is packaged with TFAM"Nucl. Acids Res.. (In press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Takamatsu et al.: "Regulation of mitochondrial D-loops by transcription factor A and single-stranded DNA-binding protein"EMBO Rep.. 3. 451-456 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohsato et al.: "Mammalian mitochondrial endonuclease G: digestion of R-loops and localization in intermembrane space"Eur. J. Biochem.. 269. 5675-5770 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iwaasa et al.: "Genomic cloning and promoter analysis of a mouse anion exchanger 3 (AE3) gene"DNA Seq.. 13. 251-255 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nagata et al.: "The regulation of DNAse activities in subcellular compartments of activated thymocytes"Immunology. 105. 399-406 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kang et al.: "Maintenance of mitochondrial DNA integrity : repair and degradation"Curr. Genet. 41. 311-322 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ide, T.et al.: "Mitochoncirial DNA damage and dysfunction associated with oxidative stress in failing hearts following myocardial infarction"Circ. Res.. 88. 529-535 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Umeda, S. et al.: "Both heavy strand replication origins are active in partially duplicated human mitochondrial DNAs"Biochem. Biophys. Res. Commun.. 286. 681-687 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tsutsui, H. et al.: "8-oxo-dGTPase, which prevents oxidative stress-induced DNA damage, increases in the mitochondria from falling hearts"Circulation. 104. 2883-2885 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Iwase, M. et al.: "Clinical features of diabetic patients with 0.01-0.1% heteroplasmy A3243G mutation in leukocyte mitochoncirial DNA"Diabetes Res Clin Pract. 54. 215-217 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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