Human heart mitochondrial DNA is organized in complex catenated networks containing abundant four-way junctions and replication forks
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Analysis of human heart mitochondrial DNA (mtDNA) by electron microscopy and agarose gel electrophoresis revealed a complete absence of the -type replication intermediates seen abundantly in mtDNA from all other tissues. Instead only Y- and X-junctional forms were detected after restriction digestion. Uncut heart mtDNA was organized in tangled complexes of up to 20 or more genome equivalents, which could be resolved to genomic monomers, dimers, and linear fragments by treatment with the decatenating enzyme topoisomerase IV plus the cruciform-cutting T7 endonuclease I. Human and mouse brain also contained a population of such mtDNA forms, which were absent, however, from mouse, rabbit, or pig heart. Overexpression in transgenic mice of two proteins involved in mtDNA replication, namely human mitochondrial transcription factor A or the mouse Twinkle DNA helicase, generated abundant four-way junctions in mtDNA of heart, brain, and skeletal muscle. The organization of mtDNA of human heart as well as of mouse and human brain in complex junctional networks replicating via a presumed non- mechanism is unprecedented in mammals.
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Systemic overexpression of Twinkle in mouse hearts causes an increase in complex DNA forms and recombination junctions similar to adult human hearts.
“Systemic overexpression of Twinkle in mouse hearts causes an increase in complex DNA forms and recombination junctions similar to adult human hearts (Pohjoismaki et al., 2009).”
From Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases (2017) · cites this paper as Pohjoismaki et al., 2009
In adult human hearts, mtDNA has been shown to exist as dimers and is organized into highly complex, branched molecules.
“In adult human hearts however, mtDNA has been shown to exist as dimers and is organized into highly complex, branched molecules (Pohjoismaki et al., 2009).”
From Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases (2017) · cites this paper as Pohjoismaki et al., 2009
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Cites
The double-strand-break repair model for recombination
Szostak, J. W., Orr-Weaver, T. L., Rothstein, R. J., & Stahl, F. W. (1983) · Cell · doi:10.1016/0092-8674(83)90331-8 · Cited by 2,437 · see citing works
Replication of animal mitochondrial DNA
Clayton, D. A. (1982) · Cell · doi:10.1016/0092-8674(82)90049-6 · Cited by 1,236 · see citing works
Mitochondrial transcription factor A regulates mtDNA copy number in mammals
Ekstrand, M. I. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh109 · Cited by 919 · see citing works
RuvAB Acts at Arrested Replication Forks
Seigneur, M., Bidnenko, V., Ehrlich, S. D., & Michel, B. (1998) · Cell · doi:10.1016/s0092-8674(00)81772-9 · Cited by 538 · see citing works
Coupled Leading- and Lagging-Strand Synthesis of Mammalian Mitochondrial DNA
Holt, I. J., Lorimer, H. E., & Jacobs, H. T. (2000) · Cell · doi:10.1016/s0092-8674(00)80688-1 · Cited by 418 · see citing works
Recombinational DNA repair and human disease
Thompson, L. H., & Schild, D. (2002) · Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis · doi:10.1016/s0027-5107(02)00224-5 · Cited by 417 · see citing works
Recombinational repair and restart of damaged replication forks
McGlynn, P., & Lloyd, R. G. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm951 · Cited by 397 · see citing works
Inheritance and recombination of mitochondrial genomes in plants, fungi and animals
Barr, C. M., Neiman, M., & TAYLOR, D. R. (2005) · New Phytologist · doi:10.1111/j.1469-8137.2005.01492.x · Cited by 386 · see citing works
THE STRUCTURE AND REPLICATION OF KINETOPLAST DNA
Shapiro, T. A., & Englund, P. T. (1995) · Annual Review of Microbiology · doi:10.1146/annurev.mi.49.100195.001001 · Cited by 369 · see citing works
Miller, F. J. (2003) · Nucleic Acids Research · doi:10.1093/nar/gng060 · Cited by 332 · see citing works
Circular Dimer and Catenate Forms of Mitochondrial DNA in Human Leukaemic Leucocytes
Clayton, D. A., & Vinograd, J. R. (1967) · Nature · doi:10.1038/216652a0 · Cited by 328 · see citing works
Multiple pathways process stalled replication forks
Michel, B., Grompone, G., Florès, M.-J., & Bidnenko, V. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401586101 · Cited by 322 · see citing works
Pathways for mitotic homologous recombination in mammalian cells
Helleday, T. (2003) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2003.08.013 · Cited by 314 · see citing works
Rescue of arrested replication forks by homologous recombination
Michel, B., Flores, M. J., Viguera, E., Grompone, G., Seigneur, M., & Bidnenko, V. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.111008798 · Cited by 292 · see citing works
Yang, M., Bowmaker, M., Reyes, A., Vergani, L., Angeli, P., Gringeri, E., Jacobs, H. T., & Holt, I. J. (2002) · Cell · doi:10.1016/s0092-8674(02)01075-9 · Cited by 275 · see citing works
Ikeuchi, M., Matsusaka, H., Kang, D., Matsushima, S., Ide, T., Kubota, T., Fujiwara, T., Hamasaki, N., Takeshita, A., Sunagawa, K., et al. (2005) · Circulation · doi:10.1161/circulationaha.104.524835 · Cited by 273 · see citing works
Mammalian Mitochondria Possess Homologous DNA Recombination Activity
Thyagarajan, B., Padua, R. A., & Campbell, C. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.44.27536 · Cited by 269 · see citing works
Yasukawa, T., Reyes, A., Cluett, T. J., Yang, M., Bowmaker, M., Jacobs, H. T., & Holt, I. J. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601392 · Cited by 251 · see citing works
Twinkle helicase is essential for mtDNA maintenance and regulates mtDNA copy number
Tyynismaa, H., Sembongi, H., Bokori-Brown, M., Granycome, C., Ashley, N., Poulton, J., Jalanko, A., Spelbrink, J. N., Holt, I. J., & Suomalainen, A. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh342 · Cited by 250 · see citing works
Unique mitochondrial genome architecture in unicellular relatives of animals
Burger, G., Forget, L., Zhu, Y. J., Gray, M. W., & Lang, B. F. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0336115100 · Cited by 221 · see citing works
Mammalian Mitochondrial DNA Replicates Bidirectionally from an Initiation Zone
Bowmaker, M., Yang, M., Yasukawa, T., Reyes, A., Jacobs, H. T., Huberman, J. A., & Holt, I. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m308028200 · Cited by 218 · see citing works
Replication of Mitochondrial DNA. Circular Replicative Intermediates in Mouse L Cells
Robberson, D. L., Kasamatsu, H., & Vinograd, J. R. (1972) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.69.3.737 · Cited by 213 · see citing works
The histone‐like protein HU binds specifically to DNA recombination and repair intermediates
Kamashev, D., & Rouvière-Yaniv, J. (2000) · EMBO Journal · doi:10.1093/emboj/19.23.6527 · Cited by 201 · see citing works
Recombination proteins and rescue of arrested replication forks
Michel, B., Boubakri, H., Baharoglu, Z., Masson, M. L., & Lestini, R. (2007) · DNA repair · doi:10.1016/j.dnarep.2007.02.016 · Cited by 197 · see citing works
RECOMBINATION AND RECOMBINATION-DEPENDENT DNA REPLICATION IN BACTERIOPHAGE T4
Mosig, G. (1998) · Annual Review of Genetics · doi:10.1146/annurev.genet.32.1.379 · Cited by 196 · see citing works
Bendich, A. J. (1996) · Journal of Molecular Biology · doi:10.1006/jmbi.1996.0048 · Cited by 191 · see citing works
Kogoma, T., Cadwell, G. W., Barnard, K. G., & Asai, T. (1996) · Journal of Bacteriology · doi:10.1128/jb.178.5.1258-1264.1996 · Cited by 180 · see citing works
Recombination associated with replication of malarial mitochondrial DNA.
Preiser, P. R., Wilson, R. J., Moore, P. W., McCready, S. J., Hajibagheri, M. A. N., Blight, K. J., Strath, M., & Williamson, D. H. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00401.x · Cited by 178 · see citing works
A Bidirectional Origin of Replication Maps to the Major Noncoding Region of Human Mitochondrial DNA
Yasukawa, T., Yang, M., Jacobs, H. T., & Holt, I. J. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.05.002 · Cited by 173 · see citing works
Sandler, S. J., Samra, H. S., & Clark, A. J. (1996) · Genetics · doi:10.1093/genetics/143.1.5 · Cited by 173 · see citing works
Pohjoismäki, J., Wanrooij, S., Hyvärinen, A. K., Goffart, S., Holt, I. J., Spelbrink, J. N., & Jacobs, H. T. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl703 · Cited by 168 · see citing works
Crews, S. T., Ojala, D., Posakony, J. W., Nishiguchi, J., & Attardi, G. M. (1979) · Nature · doi:10.1038/277192a0 · Cited by 167 · see citing works
Rolling circle replication of DNA in yeast mitochondria.
Maleszka, R., Skelly, P. J., & Clark-Walker, G. D. (1991) · The EMBO Journal · doi:10.1002/j.1460-2075.1991.tb04962.x · Cited by 164 · see citing works
Fujiwara, Y., & Tatsumi, M. (1976) · Mutation Research · doi:10.1016/0027-5107(76)90058-0 · Cited by 142 · see citing works
Most Chloroplast DNA of Maize Seedlings in Linear Molecules with Defined Ends and Branched Forms
Oldenburg, D. J., & Bendich, A. J. (2003) · Journal of Molecular Biology · doi:10.1016/j.jmb.2003.11.020 · Cited by 141 · see citing works
Robberson, D. L., & Clayton, D. A. (1972) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.69.12.3810 · Cited by 137 · see citing works
Hyvärinen, A. K., Pohjoismäki, J., Reyes, A., Wanrooij, S., Yasukawa, T., Karhunen, P. J., Spelbrink, J. N., Holt, I. J., & Jacobs, H. T. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm676 · Cited by 132 · see citing works
Akins, R. A., Kelley, R. L., & Lambowitz, A. M. (1986) · Cell · doi:10.1016/0092-8674(86)90615-x · Cited by 132 · see citing works
Zelenaya-Troitskaya, O., Newman, S. M., Okamoto, K., Perlman, P. S., & Butow, R. A. (1998) · Genetics · doi:10.1093/genetics/148.4.1763 · Cited by 131 · see citing works
Oldenburg, D. J., & Bendich, A. J. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.4783 · Cited by 122 · see citing works
Electron-microscopic visualization of deletion mutations.
Davis, R. W., & Davidson, N. (1968) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.60.1.243 · Cited by 119 · see citing works
Size and Structure of Replicating Mitochondrial DNA in Cultured Tobacco Cells.
Oldenburg, D., & Bendich, A. J. (1996) · The Plant Cell · doi:10.1105/tpc.8.3.447 · Cited by 115 · see citing works
Backert, S., & Börner, T. (2000) · Current Genetics · doi:10.1007/s002940050532 · Cited by 113 · see citing works
Late‐onset mitochondrial DNA depletion: DNA copy number, multiple deletions, and compensation
Barthélémy, C., de Baulny, H. O., Diaz, J., Cheval, M. A., Frachon, P., Romero, N. B., Goutières, F., Fardeau, M., & Lombès, A. (2001) · Annals of Neurology · doi:10.1002/ana.1002 · Cited by 109 · see citing works
The evolution of mitochondrial DNA
Saccone, C. (1994) · Current Opinion in Genetics & Development · doi:10.1016/0959-437x(94)90073-6 · Cited by 106 · see citing works
MacAlpine, D. M., Perlman, P. S., & Butow, R. A. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.12.6739 · Cited by 106 · see citing works
Heterologous mitochondrial DNA recombination in human cells
D’Aurelio, M., Gajewski, C. D., Lin, M. T. S., Mauck, W. M., Shao, L. Z., Lenaz, G., Moraes, C. T., & Manfredi, G. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh326 · Cited by 106 · see citing works
Repression of mutagenesis by Rad51D-mediated homologous recombination
Hinz, J. M. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl020 · Cited by 100 · see citing works
Lack of age-related increase of mitochondrial DNA amount in brain, skeletal muscle and human heart
Frahm, T., Mohamed, S. A., Bruse, P., Gemünd, C., Oehmichen, M., & Meißner, C. (2005) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2005.06.008 · Cited by 100 · see citing works
Prominent mitochondrial DNA recombination intermediates in human heart muscle
Kajander, O. A., Karhunen, P. J., Holt, I. J., & Jacobs, H. T. (2001) · EMBO Reports · doi:10.1093/embo-reports/kve233 · Cited by 100 · see citing works
Holt, I. J. (1997) · Human Molecular Genetics · doi:10.1093/hmg/6.8.1251 · Cited by 99 · see citing works
Replication fork regression in repetitive DNAs
Fouché, N., Özgür, S., Roy, D., & Griffith, J. D. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl757 · Cited by 98 · see citing works
Li, S., & Waters, R. (1998) · Journal of Bacteriology · doi:10.1128/jb.180.15.3750-3756.1998 · Cited by 98 · see citing works
Late‐onset mitochondrial DNA depletion: DNA copy number, multiple deletions, and compensation
Barthélémy, C., de Baulny, H. O., Diaz, J., et al. (2001) · Annals of Neurology · doi:10.1002/ana.1002.abs · Cited by 91 · see citing works
Tang, Y., Manfredi, G., Hirano, M., & Schon, E. A. (2000) · Molecular Biology of the Cell · doi:10.1091/mbc.11.7.2349 · Cited by 91 · see citing works
Bidirectional Replication Initiates at Sites Throughout the Mitochondrial Genome of Birds
Reyes, A., Yang, M., Bowmaker, M., & Holt, I. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m411916200 · Cited by 82 · see citing works
Occurrence of Complex Mitochondrial DNA in Normal Tissues
Clayton, D. A., Smith, C. A., JORDAN, J. M., Teplitz, M., & Vinograd, J. R. (1968) · Nature · doi:10.1038/220976a0 · Cited by 77 · see citing works
Drew, M. E., & Englund, P. T. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.153.4.735 · Cited by 76 · see citing works
Zsurka, G., Kraytsberg, Y., Kudina, T. A., Kornblum, C., Elger, C. E., Khrapko, K., & Kunz, W. S. (2005) · Nature Genetics · doi:10.1038/ng1606 · Cited by 66 · see citing works
Rolling-Circle Replication of Mitochondrial DNA in the Higher Plant Chenopodium album (L.)
Backert, S., Dörfel, P., Lurz, R., & Börner, T. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.11.6285 · Cited by 66 · see citing works
Replicating molecules of circular mitochondrial DNA.
Kirschner, R. H., Wolstenholme, D. R., & Gross, N. J. (1968) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.60.4.1466 · Cited by 65 · see citing works
Kong, D., & Richardson, C. C. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00552.x · Cited by 64 · see citing works
Khazi, F. R., Edmondson, A. C., & Nielsen, B. L. (2003) · Molecular Genetics and Genomics · doi:10.1007/s00438-003-0859-6 · Cited by 60 · see citing works
Jacobs, M. A., Payne, S. R., & Bendich, A. J. (1996) · Current Genetics · doi:10.1007/s002940050093 · Cited by 56 · see citing works
Role of the histone-like proteins OsmZ and HU m homologous recombination
Dri, A., Moreau, P. L., & Rouvière‐Yaniv, J. (1992) · Gene · doi:10.1016/0378-1119(92)90003-8 · Cited by 51 · see citing works
Ohno, T., Umeda, S., Hamasaki, N., & Kang, D. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.2656 · Cited by 51 · see citing works
Han, Z., & Stachow, C. (1994) · Chromosoma · doi:10.1007/bf00368008 · Cited by 49 · see citing works
Ling, F., Hori, A., & Shibata, T. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00770-06 · Cited by 49 · see citing works
Recombinational DNA repair: the ignored repair systems
Smith, K. C. (2004) · BioEssays · doi:10.1002/bies.20109 · Cited by 39 · see citing works
Size and Structure of Replicating Mitochondrial DNA in Cultured Tobacco Cells
Oldenburg, D. J., & Bendich, A. J. (1996) · The Plant Cell · doi:10.2307/3870324 · Cited by 39 · see citing works
Thresher, R., & Griffith, J. D. (1992) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(92)11026-f · Cited by 38 · see citing works
Odahara, M., Inouye, T., Fujita, T., Hasebe, M., & Sekine, Y. (2007) · Genes & Genetic Systems · doi:10.1266/ggs.82.43 · Cited by 26 · see citing works
Flagged first, then by citations
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Sorted by citations
Mitochondrial DNA mutations and human disease
Tuppen, H. A. L., Blakely, E. L., Turnbull, D. M., & Taylor, R. W. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2009.09.005 · Cited by 676 · see citing works
ER-mitochondria contacts couple mtDNA synthesis with mitochondrial division in human cells
Lewis, S. C., Uchiyama, L. F., & Nunnari, J. (2016) · Science · doi:10.1126/science.aaf5549 · Cited by 673 · see citing works
Somatic Mitochondrial DNA Mutations in Mammalian Aging
Larsson, N. (2010) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060408-093701 · Cited by 543 · see citing works
The Maintenance of Mitochondrial DNA Integrity--Critical Analysis and UpdatePreprint
ALEXEYEV, M. F., Shokolenko, I. N., Wilson, G. L., & LeDoux, S. P. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a012641 · Cited by 461 · see citing works
In D-loop: 40years of mitochondrial 7S DNA
Nicholls, T. J. J., & Minczuk, M. A. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.03.027 · Cited by 287 · see citing works
Mikhed, Y., Daiber, A., & Steven, S. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms160715918 · Cited by 257 · see citing works
DeBalsi, K. L., Hoff, K. E., & Copeland, W. C. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.04.006 · Cited by 180 · see citing works
The Mitochondrial Response to DNA Damage
Rong, Z., Tu, P., Xu, P., Sun, Y., Yu, F., Tu, N., Guo, L., & Yang, Y. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.669379 · Cited by 177 · see citing works
Human Mitochondrial DNA ReplicationPreprint
Holt, I. J., & Reyes, A. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a012971 · Cited by 155 · see citing works
Ciprofloxacin impairs mitochondrial DNA replication initiation through inhibition of Topoisomerase 2
Hangas, A., Aasumets, K., Kekäläinen, N. J., Paloheinä, M., Pohjoismäki, J., Gerhold, J. M., & Goffart, S. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky793 · Cited by 149 · see citing works
The role of mitochondria in cardiac development and protection
Pohjoismäki, J., & Goffart, S. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.02.032 · Cited by 145 · see citing works
High mitochondrial DNA copy number has detrimental effects in mice
Ylikallio, E., Tyynismaa, H., Tsutsui, H., Ide, T., & Suomalainen, A. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq163 · Cited by 137 · see citing works
The human mitochondrial replication fork in health and disease
Wanrooij, S., & Falkenberg, M. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.04.015 · Cited by 128 · see citing works
Tissue specific differences in mitochondrial DNA maintenance and expression
Herbers, E., Kekäläinen, N. J., Hangas, A., Pohjoismäki, J., & Goffart, S. (2018) · Mitochondrion · doi:10.1016/j.mito.2018.01.004 · Cited by 122 · see citing works
Therapeutic prospects for mitochondrial disease
Schon, E. A., DiMauro, S., Hirano, M., & Gilkerson, R. (2010) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2010.04.007 · Cited by 118 · see citing works
An overview of mammalian mitochondrial DNA replication mechanisms
Yasukawa, T., & Kang, D. (2018) · The Journal of Biochemistry · doi:10.1093/jb/mvy058 · Cited by 112 · see citing works
Mechanisms of Mitochondrial DNA Repair in Mammals
Zinovkina, L. A. (2018) · Biochemistry (Moscow) · doi:10.1134/s0006297918030045 · Cited by 97 · see citing works
Mitochondria–nucleus network for genome stability
Kaniak, A., & Skoneczna, A. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.01.013 · Cited by 95 · see citing works
The role of mitochondrial DNA damage in the development of atherosclerosis
Yu, E., & Bennett, M. R. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.06.011 · Cited by 90 · see citing works
PrimPol is required for replication reinitiation after mtDNA damage
Torregrosa‐Muñumer, R., Forslund, J. M. E., Goffart, S., Pfeiffer, A., Stojkovič, G., Carvalho, G., Al-Furoukh, N., Blanco, L., Wanrooij, S., & Pohjoismäki, J. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1705367114 · Cited by 88 · see citing works
Chen, X. J. (2013) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00007-13 · Cited by 85 · see citing works
Mitochondrial DNA maintenance: an appraisal
Akhmedov, A. T., & Marı́n-Garcı́a, J. (2015) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-015-2532-x · Cited by 83 · see citing works
Mitochondrial Gene Expression and Beyond—Novel Aspects of Cellular Physiology
Kotrys, A. V., & Szczęsny, R. J. (2019) · Cells · doi:10.3390/cells9010017 · Cited by 81 · see citing works
Gerhold, J. M., Aun, A., Sedman, T., Jõers, P., & Sedman, J. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.002 · Cited by 80 · see citing works
Pohjoismäki, J., & Goffart, S. (2011) · BioEssays · doi:10.1002/bies.201000137 · Cited by 71 · see citing works
Replicating animal mitochondrial DNA
McKinney, E. A., & Oliveira, M. T. (2013) · Genetics and Molecular Biology · doi:10.1590/s1415-47572013000300002 · Cited by 69 · see citing works
Dlasková, A., Špaček, T., Šantorová, J., Plecitá‐Hlavatá, L., Berková, Z., Saudek, F., Lessard, M. D., Bewersdorf, J., & Ježek, P. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.02.003 · Cited by 67 · see citing works
Kolesar, J. E., Wang, C. Y., Taguchi, Y. V., Chou, S.-H., & Kaufman, B. A. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks1324 · Cited by 62 · see citing works
Pohjoismäki, J., Boettger, T., Liu, Z., Goffart, S., Szibor, M., & Braun, T. W. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks301 · Cited by 65 · see citing works
Human mitochondrial DNA helicase TWINKLE is both an unwinding and annealing helicase
Sen, D., Nandakumar, D., Tang, G.-Q., & Patel, S. S. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.309468 · Cited by 63 · see citing works
Animal Mitochondrial DNA Replication
Ciesielski, G. L., Oliveira, M. T., & Kaguni, L. S. (2016) · The Enzymes · doi:10.1016/bs.enz.2016.03.006 · Cited by 58 · see citing works
Recombination-dependent concatemeric viral DNA replication
Piano, A. L., Martínez-Jiménez, M. I., Zecchi, L., & Ayora, S. (2011) · Virus Research · doi:10.1016/j.virusres.2011.06.009 · Cited by 59 · see citing works
Replication Stress at Telomeric and Mitochondrial DNA: Common Origins and Consequences on Ageing
Billard, P., & Poncet, D. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20194959 · Cited by 57 · see citing works
Energy substrate metabolism and oxidative stress in metabolic cardiomyopathy
Chen, Z., Jin, Z., Cai, J., Li, R., Deng, K., Ji, Y., Lei, F., Li, H., Lu, Z., & Li, H. (2022) · Journal of Molecular Medicine · doi:10.1007/s00109-022-02269-1 · Cited by 57 · see citing works
Mitochondrial DNA repair: a novel therapeutic target for heart failure
Marı́n-Garcı́a, J. (2016) · Heart Failure Reviews · doi:10.1007/s10741-016-9543-x · Cited by 54 · see citing works
Pohjoismäki, J. L. O., Goffart, S., Taylor, R. W., Turnbull, D. M., Suomalainen, A., Jacobs, H. T., & Karhunen, P. J. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010426 · Cited by 50 · see citing works
A Nuclear mtDNA Concatemer (Mega-NUMT) Could Mimic Paternal Inheritance of Mitochondrial Genome
Balciuniene, J., & Balciunas, D. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00518 · Cited by 49 · see citing works
Pohjoismäki, J. L. O., Williams, S. L., Boettger, T., Goffart, S., Kim, J., Suomalainen, A., Moraes, C. T., & Braun, T. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1303046110 · Cited by 45 · see citing works
Mgm101 Is a Rad52-related Protein Required for Mitochondrial DNA Recombination
Mbantenkhu, M., Wang, X., Nardozzi, J. D., Wilkens, S., Hoffman, E. A., Patel, A. B., Cosgrove, M. S., & Chen, X. J. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.307512 · Cited by 43 · see citing works
Lewis, S. C., Jõers, P., Willcox, S., Griffith, J. D., Jacobs, H. T., & Hyman, B. C. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1004985 · Cited by 43 · see citing works
Torregrosa-Muñumer, R., Goffart, S., Haikonen, J. A., & Pohjoismäki, J. L. O. (2015) · Molecular Biology of the Cell · doi:10.1091/mbc.e15-06-0390 · Cited by 42 · see citing works
Ruhanen, H., Ushakov, K., & Yasukawa, T. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2011.08.008 · Cited by 41 · see citing works
Pohjoismäki, J., Krüger, M., Al-Furoukh, N., Lagerstedt, A., Karhunen, P. J., & Braun, T. W. (2013) · Molecular BioSystems · doi:10.1039/c3mb25556e · Cited by 38 · see citing works
Twist and Turn—Topoisomerase Functions in Mitochondrial DNA Maintenance
Goffart, S., Hangas, A., & Pohjoismäki, J. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20082041 · Cited by 40 · see citing works
Mitochondrial DNA Copy Number and Developmental Origins of Health and Disease (DOHaD)
Fukunaga, H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126634 · Cited by 39 · see citing works
Mitochondrial DNA replication and repair defects: Clinical phenotypes and therapeutic interventions
Roy, A., Kandettu, A., Ray, S., & Chakrabarty, S. (2022) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2022.148554 · Cited by 38 · see citing works
Controlling the topology of mammalian mitochondrial DNA
Menger, K. E., Rodríguez‐Luis, A., Chapman, J., & Nicholls, T. J. J. (2021) · Open Biology · doi:10.1098/rsob.210168 · Cited by 38 · see citing works
DNA topoisomerases in mtDNA maintenance and ageing
Sobek, S., & Boege, F. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.01.009 · Cited by 38 · see citing works
Unique features of DNA replication in mitochondria: A functional and evolutionary perspective
Holt, I. J., & Jacobs, H. T. (2014) · BioEssays · doi:10.1002/bies.201400052 · Cited by 36 · see citing works
Human Rad51 promotes mitochondrial DNA synthesis under conditions of increased replication stress
Sage, J. M., & Knight, K. L. (2013) · Mitochondrion · doi:10.1016/j.mito.2013.04.004 · Cited by 36 · see citing works
35 Years of TFAM Research: Old Protein, New Puzzles
Kozhukhar, N., & ALEXEYEV, M. F. (2023) · Biology · doi:10.3390/biology12060823 · Cited by 35 · see citing works
The Regulation of Homologous Recombination by Helicases
Huselid, E., & Bunting, S. F. (2020) · Genes · doi:10.3390/genes11050498 · Cited by 35 · see citing works
Release of damaged mitochondrial DNA: A novel factor in stimulating inflammatory response
Li, W., Li, Y., Zhao, J., Liao, J., Wen, W., Chen, Y., & Cui, H. (2024) · Pathology - Research and Practice · doi:10.1016/j.prp.2024.155330 · Cited by 34 · see citing works
Animal models of mitochondrial DNA transactions in disease and ageing
Oliveira, M. T., Garesse, R., & Kaguni, L. S. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2010.01.019 · Cited by 33 · see citing works
Unveiling the mystery of mitochondrial DNA replication in yeasts
Chen, X. J., & Clark-Walker, G. D. (2017) · Mitochondrion · doi:10.1016/j.mito.2017.07.009 · Cited by 33 · see citing works
Gerhold, J. M., Sedman, T., Visacka, K., Slezakova, J., Tomáška, Ľ., Nosek, J., & Sedman, J. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.552828 · Cited by 30 · see citing works
Sharbrough, J., Bankers, L., Cook, E., Fields, P. D., Jalinsky, J., McElroy, K. E., Neiman, M., Logsdon, J. M., Jr., & Boore, J. L. (2023) · Molecular Biology and Evolution · doi:10.1093/molbev/msad007 · Cited by 30 · see citing works
HMGA1 Levels Influence Mitochondrial Function and Mitochondrial DNA Repair Efficiency
Mao, L., Wertzler, K. J., Maloney, S. C., Wang, Z., Magnuson, N. S., & Reeves, R. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00105-09 · Cited by 30 · see citing works
Homologous DNA strand exchange activity of the human mitochondrial DNA helicase TWINKLE
Sen, D., Patel, G., & Patel, S. S. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw098 · Cited by 30 · see citing works
Evolving mtDNA populations within cells
Johnston, I. G., & Burgstaller, J. P. (2019) · Biochemical Society Transactions · doi:10.1042/bst20190238 · Cited by 29 · see citing works
Enzymology of mitochondrial DNA repair
Alencar, R. R., Batalha, C. M. P. F., Freire, T. S., & de Souza-Pinto, N. C. (2019) · The Enzymes · doi:10.1016/bs.enz.2019.06.002 · Cited by 27 · see citing works
Kelm, J. M., Samarbakhsh, A., Pillai, A., VanderVere-Carozza, P. S., Aruri, H., Pandey, D. S., Pawelczak, K. S., Turchi, J. J., & Gavande, N. S. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.850883 · Cited by 26 · see citing works
Top3α is the replicative topoisomerase in mitochondrial DNA replication
Hangas, A., Kekäläinen, N. J., Potter, A., Michell, C., Aho, K. J., Rutanen, C., Spelbrink, J. N., Pohjoismäki, J., & Goffart, S. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac660 · Cited by 26 · see citing works
Cluett, T. J., Akman, G., Reyes, A., Kazak, L., Mitchell, A., Wood, S., Spinazzola, A., Spelbrink, J. N., & Holt, I. J. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky852 · Cited by 26 · see citing works
Structure, function and evolution of the animal mitochondrial replicative DNA helicase
Kaguni, L. S., & Oliveira, M. T. (2015) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2015.1117056 · Cited by 25 · see citing works
Pohjoismäki, J., Goffart, S., & Spelbrink, J. N. (2011) · Mitochondrion · doi:10.1016/j.mito.2011.04.002 · Cited by 23 · see citing works
Replication fork rescue in mammalian mitochondria
Torregrosa‐Muñumer, R., Hangas, A., Goffart, S., Blei, D., Zsurka, G., Griffith, J. D., Kunz, W. S., & Pohjoismäki, J. (2019) · Scientific Reports · doi:10.1038/s41598-019-45244-6 · Cited by 23 · see citing works
Dynamic Localization of Trypanosoma brucei Mitochondrial DNA Polymerase ID
Concepción‐Acevedo, J., Luo, J., & Klingbeil, M. M. (2012) · Eukaryotic Cell · doi:10.1128/ec.05291-11 · Cited by 23 · see citing works
Biochemical Characterization of the Human Mitochondrial Replicative Twinkle Helicase
Khan, I., Crouch, J. D., Bharti, S. K., Sommers, J. A., Carney, S. M., Yakubovskaya, E., García–Díaz, M., Trakselis, M. A., & Brosh, R. M. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.712026 · Cited by 23 · see citing works
Martinez, C., Zheng, A., & Xiao, Q. (2024) · Antioxidants · doi:10.3390/antiox13111330 · Cited by 26 · see citing works
Raap, A. K., Tafrechi, R. S. J., van de Rijke, F. M., Pyle, A., Wählby, C., Szuhai, K., Ravelli, R. B. G., de Coo, I. F. M., Rajasimha, H. K., Nilsson, M. F., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0052080 · Cited by 21 · see citing works
Jõers, P., Lewis, S. C., Fukuoh, A., Parhiala, M., Ellilä, S., Holt, I. J., & Jacobs, H. T. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003800 · Cited by 19 · see citing works
Known Unknowns of Mammalian Mitochondrial DNA Maintenance
Pohjoismäki, J., Forslund, J. M. E., Goffart, S., Torregrosa‐Muñumer, R., & Wanrooij, S. (2018) · BioEssays · doi:10.1002/bies.201800102 · Cited by 18 · see citing works
Roles of the mitochondrial replisome in mitochondrial DNA deletion formation
Oliveira, M. T., Pontes, C. D. B., & Ciesielski, G. L. (2020) · Genetics and Molecular Biology · doi:10.1590/1678-4685-gmb-2019-0069 · Cited by 18 · see citing works
Vozáriková, V., Kunová, N., Bauer, J., Frankovský, J., Kotrasová, V., Procházková, K., Džugasová, V., Kutějová, E., Pevala, V., Nosek, J., et al. (2020) · Biomolecules · doi:10.3390/biom10081193 · Cited by 18 · see citing works
Phosphoproteomics of the developing heart identifies PERM1 - An outer mitochondrial membrane protein
Aravamudhan, S., Türk, C., Bock, T., Keufgens, L., Nolte, H., Lang, F., Krishnan, R. K., König, T., Hammerschmidt, P., Schindler, N., et al. (2021) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2021.01.010 · Cited by 18 · see citing works
Khatib, I. A., Deng, J., Symes, A., Kerr, M., Zhang, H., Huang, S.-Y. N., Pommier, Y. G., Khan, A., & Shutt, T. E. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102420 · Cited by 17 · see citing works
The DNA damage response is developmentally regulated in the African trypanosome
Vieira‐da‐Rocha, J. P., Passos-Silva, D. G., Mendes, I. C., Rocha, E. A., Gomes, D. A., Machado, C. R., & McCulloch, R. (2018) · DNA repair · doi:10.1016/j.dnarep.2018.11.005 · Cited by 16 · see citing works
The road to rack and ruin: selecting deleterious mitochondrial DNA variants
Holt, I. J., Speijer, D., & Kirkwood, T. B. L. (2014) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2013.0451 · Cited by 14 · see citing works
The mitochondrial genome. The nucleoid
Kolesnikov, A. (2016) · Biochemistry (Moscow) · doi:10.1134/s0006297916100047 · Cited by 16 · see citing works
Evolution and maintenance of mtDNA gene content across eukaryotes
Veeraragavan, S., Johansen, M., & Johnston, I. G. (2024) · Biochemical Journal · doi:10.1042/bcj20230415 · Cited by 15 · see citing works
Enlightenment of Yeast Mitochondrial Homoplasmy: Diversified Roles of Gene Conversion
Ling, F., Mikawa, T., & Shibata, T. (2011) · Genes · doi:10.3390/genes2010169 · Cited by 15 · see citing works
Yazdani, M. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-03938-7 · Cited by 14 · see citing works
Linear DNA-driven recombination in mammalian mitochondria
Fragkoulis, G., Hangas, A., Fekete, Z., Michell, C., Moraes, C. T., Willcox, S., Griffith, J. D., Goffart, S., & Pohjoismäki, J. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae040 · Cited by 14 · see citing works
Complex Interplay between DNA Damage and Autophagy in Disease and Therapy
Singh, A. D., Ravendranathan, N., Frisbee, J. C., & Singh, K. K. (2024) · Biomolecules · doi:10.3390/biom14080922 · Cited by 14 · see citing works
Mitochondrial matrix processes
Mazunin, I., Левицкий, С. А., Patrushev, M. V., & Kamenski, P. A. (2015) · Biochemistry (Moscow) · doi:10.1134/s0006297915110036 · Cited by 14 · see citing works
Short‐range inversions: Rethinking organelle genome stability
Tremblay‐Belzile, S., Lepage, É., Zampini, É., & Brisson, N. (2015) · BioEssays · doi:10.1002/bies.201500064 · Cited by 13 · see citing works
Mitochondrial cardiomyopathies: pathogenesis, diagnosis, and treatment
Maack, C., Dudek, J., Bertero, E., Tampakakis, E., & Vernon, H. J. (2025) · European Heart Journal · doi:10.1093/eurheartj/ehaf491 · Cited by 12 · see citing works
DNA Replication in Human Mitochondria
Zinovkina, L. A. (2019) · Biochemistry (Moscow) · doi:10.1134/s0006297919080042 · Cited by 12 · see citing works
Mitochondrial Genome Evolution
Bernt, M., Machné, R., Sahyoun, A. H., Middendorf, M., & Stadler, P. F. (2013) · Encyclopedia of Life Sciences · doi:10.1002/9780470015902.a0025142 · Cited by 12 · see citing works
Ciesielski, G. L., Nadalutti, C. A., Oliveira, M. T., Jacobs, H. T., Griffith, J. D., & Kaguni, L. S. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky094 · Cited by 11 · see citing works
Ling, F., & Yoshida, M. (2020) · Genes · doi:10.3390/genes11050514 · Cited by 11 · see citing works
Niu, R., Yoshida, M., & Ling, F. (2012) · PLoS ONE · doi:10.1371/journal.pone.0040572 · Cited by 11 · see citing works
Palacios, B. S., Villares, R., Lucas, P., Rodrı́guez-Frade, J. M., Cayuela, A., Piccirillo, J., Lombardía, M., Gestoso, D. D., Fernández-García, M., Risco, C., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1200259 · Cited by 10 · see citing works
Herbers, E., Patrikoski, M., Wagner, A., Jokinen, R., Hassinen, A., Heinonen, S., Miettinen, S., Peltoniemi, H. H., Pirinen, E., & Pietiläinen, K. H. (2022) · Stem Cells International · doi:10.1155/2022/3308194 · Cited by 10 · see citing works
TOP3A coupling with replication forks and repair of TOP3A cleavage complexes
Saha, L. K., & Pommier, Y. G. (2024) · Cell Cycle · doi:10.1080/15384101.2024.2314440 · Cited by 9 · see citing works
The Role of DNA Repair in Maintaining Mitochondrial DNA Stability
Zhang, L., Reyes, A., & Wang, X. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-981-10-6674-0_7 · Cited by 9 · see citing works
Natural and Artificial Mechanisms of Mitochondrial Genome Elimination
Zakirova, E. G., Muzyka, V. V., Mazunin, I., & Orishchenko, К. E. (2021) · Life · doi:10.3390/life11020076 · Cited by 8 · see citing works
Disruption of mitochondrial DNA integrity in cardiomyocyte injury upon ischemia/reperfusion
Hu, S., Tang, X., Zhu, F., Chen, L., Wang, S., Wang, H., Li, P., & Li, Y. (2024) · Genes & Diseases · doi:10.1016/j.gendis.2024.101282 · Cited by 7 · see citing works
Young, M. J., Sachidanandam, R., Hales, D. B., Brard, L., Robinson, K., Rahman, M. M., Khadka, P., Groesch, K. A., & Young, C. K. J. (2022) · Life · doi:10.3390/life12040562 · Cited by 7 · see citing works
- Authors
- Pohjoismäki, J. L. O., Goffart, S., Tyynismaa, H., Willcox, S., Ide, T., Kang, D., Suomalainen, A., Karhunen, P. J., Griffith, J. D., Holt, I. J., & Jacobs, H. T.
- Affiliations
- Tampere University Hospital (FI)
- University of Helsinki (FI)
- University of North Carolina at Chapel Hill (US)
- Kyushu University (JP)
- University of Tampere (FI)
- MRC Mitochondrial Biology Unit (GB)
- Corresponding author
- Jacobs, Howard T.
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2009-08
- Volume
- 284
- Issue
- 32
- Pages
- 21446-21457
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2755869
- OpenAlex
- W2014114000
- Cited by
- 122
- References
- 70
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 9 · 2023: 4 · 2022: 8 · 2021: 6 · 2020: 8 · 2019: 10 · 2018: 10 · 2017: 4 · 2016: 8 · 2015: 10 · 2014: 5 · 2013: 9 · 2012: 10
- FWCI
- 3.89
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- UNC Libraries
- Funders
- Foundation for Cardiovascular Research
- European Commission
- Academy of Finland
- Suomen Kulttuurirahasto
- Sydäntutkimussäätiö
- Tays
- National Institutes of Health
- Medical Research Council
- National Institute of General Medical Sciences (GM-31819, R01GM031819)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- mitochondrial DNA, heart, four-way junction, replication fork, topoisomerase IV, T7 endonuclease I, TFAM, Twinkle helicase, mitochondrial DNA replication, brain, skeletal muscle, species differences
- MeSH terms
- Adult, Aged, Animals, Brain, Child, Preschool, DNA, Mitochondrial, Female, Heart, Humans, Male, Mice, Transgenic, Middle Aged, Nucleic Acid Conformation, Rabbits, Species Specificity, Swine, Tissue Distribution, Mice
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