Strand-asynchronous mitochondrial DNA replication
Falkenberg M, Larsson NG, Gustafsson CM. Replication and Transcription of Human Mitochondrial DNA. Annu Rev Biochem. 2024 Aug;93(1):47–77. doi: 10.1146/annurev-biochem-052621-092014. PMID: 38594940.; Plaza-G A I, Lemishko KM, Crespo R, Truong TQ, Kaguni LS, Cao-García FJ, Ciesielski GL, Ibarra B. Mechanism of strand displacement DNA synthesis by the coordinated activities of human mitochondrial DNA polymerase and SSB. Nucleic Acids Res. 2023 Feb 27;51(4):1750–65. PMID: 36744436; PMCID: PMC9976888.; Misic J, Milenkovic D, Al-Behadili A, Xie X, Jiang M, Jiang S, Filograna R, Koolmeister C, Siira SJ, Jenninger L, Filipovska A, Clausen AR, Caporali L, Valentino ML, La Morgia C, Carelli V, Nicholls TJ, Wredenberg A, Falkenberg M, Larsson NG. Mammalian RNase H1 directs RNA primer formation for mtDNA replication initiation and is also necessary for mtDNA replication completion. Nucleic Acids Res. 2022 Aug 26;50(15):8749–66. PMID: 35947649; PMCID: PMC9410905.; Karlowicz A, Dubiel AB, Czerwinska J, Bledea A, Purzycki P, Grzelewska M, McAuley RJ, Szczesny RJ, Brzuska G, Krol E, Szczesny B, Szymanski MR. In vitro reconstitution reveals a key role of human mitochondrial EXOG in RNA primer processing. Nucleic Acids Res. 2022 Aug 12;50(14):7991–8007. PMID: 35819194; PMCID: PMC9371904.; Shokolenko I, Alexeyev M. Mitochondrial DNA: Consensuses and Controversies. DNA (Basel). 2022 Jun;2(2):131–48. PMID: 36381197; PMCID: PMC9648901.; Kosar M, Piccini D, Foiani M, Giannattasio M. A rapid method to visualize human mitochondrial DNA replication through rotary shadowing and transmission electron microscopy. Nucleic Acids Res. 2021 Dec 02;49(21):e121. PMID: 34500456; PMCID: PMC8643652.; Kaur P, Pan H, Longley MJ, Copeland WC, Wang H. Using Atomic Force Microscopy to Study the Real Time Dynamics of DNA Unwinding by Mitochondrial Twinkle Helicase. Bio Protoc. 2021 Sep 05;11(17):e4139. PMID: 34604445; PMCID: PMC8443461.; Sarfallah A, Zamudio-Ochoa A, Anikin M, Temiakov D. Mechanism of transcription initiation and primer generation at the mitochondrial replication origin OriL. EMBO J. 2021 Oct 01;40(19):e107988. PMID: 34423452; PMCID: PMC8488568.; Uhler JP, Falkenberg M. In Vitro Analysis of mtDNA Replication. Methods Mol Biol. 2021;2192():1–20. doi: 10.1007/978-1-0716-0834-0_1. PMID: 33230761.; Kaur P, Longley MJ, Pan H, Wang W, Countryman P, Wang H, Copeland WC. Single-molecule level structural dynamics of DNA unwinding by human mitochondrial Twinkle helicase. Journal of Biological Chemistry. 2020 Apr;295(17):5564–76. doi: 10.1074/jbc.ra120.012795.; Peter B, Falkenberg M. TWINKLE and Other Human Mitochondrial DNA Helicases: Structure, Function and Disease. Genes (Basel). 2020 Apr 09;11(4). PMID: 32283748; PMCID: PMC7231222.; Wu CC, Lin JLJ, Yang-Yen HF, Yuan HS. A unique exonuclease ExoG cleaves between RNA and DNA in mitochondrial DNA replication. Nucleic Acids Res. 2019 Jun 04;47(10):5405–19. PMID: 30949702; PMCID: PMC6547421.; Posse V, Al-Behadili A, Uhler JP, Clausen AR, Reyes A, Zeviani M, Falkenberg M, Gustafsson CM. RNase H1 directs origin-specific initiation of DNA replication in human mitochondria. PLoS Genet. 2019 Jan 03;15(1):e1007781. doi: 10.1371/journal.pgen.1007781.; Kaur P, Longley MJ, Pan H, Wang H, Copeland WC. Single-molecule DREEM imaging reveals DNA wrapping around human mitochondrial single-stranded DNA binding protein. Nucleic Acids Res. 2018 Nov 30;46(21):11287–302. PMID: 30256971; PMCID: PMC6265486.; Cluett TJ, Akman G, Reyes A, Kazak L, Mitchell A, Wood SR, Spinazzola A, Spelbrink JN, Holt IJ. Transcript availability dictates the balance between strand-asynchronous and strand-coupled mitochondrial DNA replication. Nucleic Acids Res. 2018 Nov 16;46(20):10771–81. PMID: 30239839; PMCID: PMC6237803.; Al-Behadili A, Uhler JP, Berglund AK, Peter B, Doimo M, Reyes A, Wanrooij S, Zeviani M, Falkenberg M. A two-nuclease pathway involving RNase H1 is required for primer removal at human mitochondrial OriL. Nucleic Acids Res. 2018 Oct 12;46(18):9471–83. PMID: 30102370; PMCID: PMC6182146.; Yasukawa T, Kang D. An overview of mammalian mitochondrial DNA replication mechanisms. J Biochem. 2018 Sep 01;164(3):183–93. PMID: 29931097; PMCID: PMC6094444.; Falkenberg M. Mitochondrial DNA replication in mammalian cells: overview of the pathway. Essays Biochem. 2018 Jul 20;62(3):287–96. PMID: 29880722; PMCID: PMC6056714.; Nicholls TJ, Nadalutti CA, Motori E, Sommerville EW, Gorman GS, Basu S, Hoberg E, Turnbull DM, Chinnery PF, Larsson N, Larsson E, Falkenberg M, Taylor RW, Griffith JD, Gustafsson CM. Topoisomerase 3a Is Required for Decatenation and Segregation of Human mtDNA. Molecular Cell. 2018 Jan;69(1):9–23.e6. doi: 10.1016/j.molcel.2017.11.033.; Uhler JP, Thörn C, Nicholls TJ, Matic S, Milenkovic D, Gustafsson CM, Falkenberg M. MGME1 processes flaps into ligatable nicks in concert with DNA polymerase ? during mtDNA replication. Nucleic Acids Res. 2016 Jul 08;44(12):5861–71. PMID: 27220468; PMCID: PMC4937333.; Uhler JP, Falkenberg M. Primer removal during mammalian mitochondrial DNA replication. DNA Repair (Amst). 2015 Oct;34():28–38. doi: 10.1016/j.dnarep.2015.07.003. PMID: 26303841.; Jemt E, Persson Ö, Shi Y, Mehmedovic M, Uhler JP, Dávila López M, Freyer C, Gustafsson CM, Samuelsson T, Falkenberg M. Regulation of DNA replication at the end of the mitochondrial D-loop involves the helicase TWINKLE and a conserved sequence element. Nucleic Acids Res. 2015 Oct 30;43(19):9262–75. PMID: 26253742; PMCID: PMC4627069.; Agaronyan K, Morozov YI, Anikin M, Temiakov D. Mitochondrial biology. Replication-transcription switch in human mitochondria. Science. 2015 Jan 30;347(6221):548–51. PMID: 25635099; PMCID: PMC4677687.; Miralles Fusté J, Shi Y, Wanrooij S, Zhu X, Jemt E, Persson Ö, Sabouri N, Gustafsson CM, Falkenberg M. In Vivo Occupancy of Mitochondrial Single-Stranded DNA Binding Protein Supports the Strand Displacement Mode of DNA Replication. PLoS Genet. 2014 Dec 04;10(12):e1004832. doi: 10.1371/journal.pgen.1004832.; Reyes A, Kazak L, Wood SR, Yasukawa T, Jacobs HT, Holt IJ. Mitochondrial DNA replication proceeds via a 'bootlace' mechanism involving the incorporation of processed transcripts. Nucleic Acids Res. 2013 Jun;41(11):5837–50. PMID: 23595151; PMCID: PMC3675460.; Wanrooij S, Miralles Fusté J, Stewart JB, Wanrooij PH, Samuelsson T, Larsson N, Gustafsson CM, Falkenberg M. In vivo mutagenesis reveals that OriL is essential for mitochondrial DNA replication. EMBO Reports. 2012 Oct 23;13(12):1130–7. doi: 10.1038/embor.2012.161.; Wanrooij PH, Uhler JP, Shi Y, Westerlund F, Falkenberg M, Gustafsson CM. A hybrid G-quadruplex structure formed between RNA and DNA explains the extraordinary stability of the mitochondrial R-loop. Nucleic Acids Res. 2012 Nov 01;40(20):10334–44. PMID: 22965135; PMCID: PMC3488243.; Kasiviswanathan R, Collins TRL, Copeland WC. The interface of transcription and DNA replication in the mitochondria. Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. 2012 Sep;1819(9-10):970–8. doi: 10.1016/j.bbagrm.2011.12.005.; Ruhanen H, Ushakov K, Yasukawa T. Involvement of DNA ligase III and ribonuclease H1 in mitochondrial DNA replication in cultured human cells. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 2011 Dec;1813(12):2000–7. doi: 10.1016/j.bbamcr.2011.08.008.; Jemt E, Farge G, Bäckström S, Holmlund T, Gustafsson CM, Falkenberg M. The mitochondrial DNA helicase TWINKLE can assemble on a closed circular template and support initiation of DNA synthesis. Nucleic Acids Res. 2011 Nov;39(21):9238–49. PMID: 21840902; PMCID: PMC3241658.; Wanrooij PH, Uhler JP, Simonsson T, Falkenberg M, Gustafsson CM. G-quadruplex structures in RNA stimulate mitochondrial transcription termination and primer formation. Proc Natl Acad Sci U S A. 2010 Sep 14;107(37):16072–7. PMID: 20798345; PMCID: PMC2941323.; Fusté JM, Wanrooij S, Jemt E, Granycome CE, Cluett TJ, Shi Y, Atanassova N, Holt IJ, Gustafsson CM, Falkenberg M. Mitochondrial RNA polymerase is needed for activation of the origin of light-strand DNA replication. Mol Cell. 2010 Jan 15;37(1):67–78. doi: 10.1016/j.molcel.2009.12.021. PMID: 20129056.; Wanrooij S, Fusté JM, Farge G, Shi Y, Gustafsson CM, Falkenberg M. Human mitochondrial RNA polymerase primes lagging-strand DNA synthesis in vitro. Proc. Natl. Acad. Sci. U.S.A. 2008 Aug 12;105(32):11122–7. doi: 10.1073/pnas.0805399105.; Pham XH, Farge G, Shi Y, Gaspari M, Gustafsson CM, Falkenberg M. Conserved Sequence Box II Directs Transcription Termination and Primer Formation in Mitochondria. Journal of Biological Chemistry. 2006 Aug;281(34):24647–52. doi: 10.1074/jbc.m602429200.; Brown TA, Cecconi C, Tkachuk AN, Bustamante C, Clayton DA. Replication of mitochondrial DNA occurs by strand displacement with alternative light-strand origins, not via a strand-coupled mechanism. Genes Dev. 2005 Oct 15;19(20):2466–76. PMID: 16230534; PMCID: PMC1257401.; Korhonen JA, Pham XH, Pellegrini M, Falkenberg M. Reconstitution of a minimal mtDNA replisome in vitro. EMBO J. 2004 Jun 16;23(12):2423–9. PMID: 15167897; PMCID: PMC423294.; Yang MY, Bowmaker M, Reyes A, Vergani L, Angeli P, Gringeri E, Jacobs HT, Holt IJ. Biased incorporation of ribonucleotides on the mitochondrial L-strand accounts for apparent strand-asymmetric DNA replication. Cell. 2002 Nov 15;111(4):495–505. doi: 10.1016/s0092-8674(02)01075-9. PMID: 12437923.; Johnson AA, Tsai Yc, Graves SW, Johnson KA. Human mitochondrial DNA polymerase holoenzyme: reconstitution and characterization. Biochemistry. 2000 Feb 22;39(7):1702–8. doi: 10.1021/bi992104w. PMID: 10677218.; Kang D, Miyako K, Kai Y, Irie T, Takeshige K. In Vivo Determination of Replication Origins of Human Mitochondrial DNA by Ligation-mediated Polymerase Chain Reaction. Journal of Biological Chemistry. 1997 Jun;272(24):15275–9. doi: 10.1074/jbc.272.24.15275.; Xu B, Clayton DA. RNA-DNA hybrid formation at the human mitochondrial heavy-strand origin ceases at replication start sites: an implication for RNA-DNA hybrids serving as primers. The EMBO Journal. 1996 Jun;15(12):3135–43. doi: 10.1002/j.1460-2075.1996.tb00676.x.; Chang DD, Clayton DA. Priming of human mitochondrial DNA replication occurs at the light-strand promoter. Proc Natl Acad Sci U S A. 1985 Jan;82(2):351–5. PMID: 2982153; PMCID: PMC397036.