Online citations, reference lists, and bibliographies.

Mitochondrial DNA Replication Proceeds Via A ‘bootlace’ Mechanism Involving The Incorporation Of Processed Transcripts

A. Reyes, L. Kazak, S. R. Wood, T. Yasukawa, H. T. Jacobs, I. Holt
Published 2013 · Medicine, Biology

Cite This
Download PDF
Analyze on Scholarcy
Share
The observation that long tracts of RNA are associated with replicating molecules of mitochondrial DNA (mtDNA) suggests that the mitochondrial genome of mammals is copied by an unorthodox mechanism. Here we show that these RNA-containing species are present in living cells and tissue, based on interstrand cross-linking. Using DNA synthesis in organello, we demonstrate that isolated mitochondria incorporate radiolabeled RNA precursors, as well as DNA precursors, into replicating DNA molecules. RNA-containing replication intermediates are chased into mature mtDNA, to which they are thus in precursor–product relationship. While a DNA chain terminator rapidly blocks the labeling of mitochondrial replication intermediates, an RNA chain terminator does not. Furthermore, processed L-strand transcripts can be recovered from gel-extracted mtDNA replication intermediates. Therefore, instead of concurrent DNA and RNA synthesis, respectively, on the leading and lagging strands, preformed processed RNA is incorporated as a provisional lagging strand during mtDNA replication. These findings indicate that RITOLS is a physiological mechanism of mtDNA replication, and that it involves a ‘bootlace' mechanism, in which processed transcripts are successively hybridized to the lagging-strand template, as the replication fork advances.
This paper references
Expression of the cytochrome b-URF6URF5 region of the mouse mitochondrial
K. S. Bhat (1985)
Annu. Rev. Biochem
D N Frick (2001)
EMBO J
10.1016/S0074-7696(08)61373-X
Animal mitochondrial DNA: an extreme example of genetic economy.
G. Attardi (1985)
10.4161/cc.9.13.12122
What happens when replication and transcription complexes collide?
Richard T Pomerantz (2010)
10.1016/0092-8674(82)90049-6
Replication of animal mitochondrial DNA
D. Clayton (1982)
10.1016/S0092-8674(00)80688-1
Coupled Leading- and Lagging-Strand Synthesis of Mammalian Mitochondrial DNA
I. Holt (2000)
10.1038/sj.emboj.7601392
Replication of vertebrate mitochondrial DNA entails transient ribonucleotide incorporation throughout the lagging strand
T. Yasukawa (2006)
10.1016/0304-4165(91)90223-4
Antibodies against DNA-psoralen crosslink recognize unique conformation.
R. Hasan (1991)
10.1016/0022-2836(77)90265-0
Photochemical cross-linking of DNA-RNA helices by psoralen derivatives.
Clifton Kwang-Fu Shen (1977)
10.1093/NAR/GKM676
The mitochondrial transcription termination factor mTERF modulates replication pausing in human mitochondrial DNA
Anne K. Hyvärinen (2007)
10.1016/J.BBAEXP.2004.12.006
Transcription arrest caused by long nascent RNA chains.
T. Bentin (2005)
The pattern of transcription of the human mitochondrial rRNA genes reveals two overlapping transcription units
G. Attardi (1983)
10.1074/JBC.M401643200
Drosophila Mitochondrial Transcription Factor B2 Regulates Mitochondrial DNA Copy Number and Transcription in Schneider Cells*
Y. Matsushima (2004)
10.1016/j.molcel.2009.12.021
Mitochondrial RNA polymerase is needed for activation of the origin of light-strand DNA replication.
Javier Miralles Fusté (2010)
10.1038/newbio241103a0
Unidirectionality of replication in mouse mitochondrial DNA.
H. Kasamatsu (1973)
10.1016/j.jmb.2010.02.029
Mammalian mitochondrial DNA replication intermediates are essentially duplex but contain extensive tracts of RNA/DNA hybrid.
J. Pohjoismäki (2010)
10.1093/nar/gks266
Mitochondrial nucleoid interacting proteins support mitochondrial protein synthesis
J. He (2012)
10.1128/9781555817480_ch7
DNA replication.
M. Gefter (1975)
10.1038/ng2040
Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion
A. Bourdon (2007)
10.1038/sj.emboj.7600257
Reconstitution of a minimal mtDNA replisome in vitro
Jenny A Korhonen (2004)
10.1074/jbc.M308028200
Mammalian Mitochondrial DNA Replicates Bidirectionally from an Initiation Zone*
Mark Bowmaker (2003)
10.1007/978-1-59745-521-3_2
Analysis of mitochondrial DNA by two-dimensional agarose gel electrophoresis.
Aurelio Reyes (2009)
10.1093/nar/gkv947
Nucleic Acids Research
K. Otto (2015)
10.1093/NAR/22.10.1861
Highly efficient DNA synthesis in isolated mitochondria from rat liver.
J. Enríquez (1994)
10.1074/JBC.M411916200
Bidirectional Replication Initiates at Sites Throughout the Mitochondrial Genome of Birds*
A. Reyes (2005)
10.1021/bi00342a020
Expression of the cytochrome b-URF6-URF5 region of the mouse mitochondrial genome.
K. S. Bhat (1985)
Human mitochondrial RNA polymerase Nucleic Acids Research, 2013, Vol. 41, No. 11 5849 primes lagging-strand DNA synthesis in vitro
S. Wanrooij (2008)
10.1016/S0092-8674(02)01075-9
Biased Incorporation of Ribonucleotides on the Mitochondrial L-Strand Accounts for Apparent Strand-Asymmetric DNA Replication
M. Y. Yang (2002)
10.1146/annurev.bi.53.070184.003041
Transcription of the mammalian mitochondrial genome.
D. Clayton (1984)
10.1038/277192a0
Nucleotide sequence of a region of human mitochondrial DNA containing the precisely identified origin of replication
S. Crews (1979)
Expression of the cytochrome b - URF 6 - URF 5 region of the mouse mitochondrial genome
J. Montoya (1985)
10.1016/J.MOLCEL.2005.05.002
A bidirectional origin of replication maps to the major noncoding region of human mitochondrial DNA.
T. Yasukawa (2005)
Mechanism of replication of human mitochondrial DNA. Localization of the 5' ends of nascent daughter strands.
D. Tapper (1981)
10.1016/0076-6879(95)62048-6
Analysis of replication intermediates by two-dimensional agarose gel electrophoresis.
K. L. Friedman (1995)
Replication of animal mitochondrial DNA
H. Kasamatsu (1982)
10.1128/MCB.16.9.4923
Characterizing replication intermediates in the amplified CHO dihydrofolate reductase domain by two novel gel electrophoretic techniques.
R. Kalejta (1996)
10.1093/NAR/GKG739
Revisiting the mouse mitochondrial DNA sequence.
M. P. Bayona-Bafaluy (2003)
10.1038/ng751
Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion myopathy
Ann Saada (2001)
10.1093/nar/gks1324
Two-dimensional intact mitochondrial DNA agarose electrophoresis reveals the structural complexity of the mammalian mitochondrial genome
J. E. Kolesar (2013)
10.1016/0092-8674(83)90145-9
The pattern of transcription of the human mitochondrial rRNA genes reveals two overlapping transcription units
Julio Montoya (1983)
10.1007/BF02602930
The complete nucleotide sequence of theRattus norvegicus mitochondrial genome: Cryptic signals revealed by comparative analysis between vertebrates
G. Gadaleta (2007)
10.1038/290457a0
Sequence and organization of the human mitochondrial genome
S. Anderson (1981)
10.1093/nar/gkm215
Expression of catalytic mutants of the mtDNA helicase Twinkle and polymerase POLG causes distinct replication stalling phenotypes
S. Wanrooij (2007)
10.1016/0968-0004(92)90410-B
DNA replication, 2nd edn
D. J. Lilley (1992)
Human mitochondrial RNA polymerase
S. Wanrooij (2008)
10.1146/annurev.biochem.70.1.39
DNA primases.
D. Frick (2001)
10.1073/pnas.0805399105
Human mitochondrial RNA polymerase primes lagging-strand DNA synthesis in vitro
S. Wanrooij (2008)
10.1016/0165-2478(95)02474-3
Native DNA fragments photocrosslinked to psoralen binds to anti-B and anti-Z DNA antibodies.
S. Arjumand (1995)



This paper is referenced by
10.1371/journal.pgen.1006628
Nucleotide pools dictate the identity and frequency of ribonucleotide incorporation in mitochondrial DNA
Anna-Karin Berglund (2017)
10.1093/nar/gkx633
Engineering human PrimPol into an efficient RNA-dependent-DNA primase/polymerase
Rubén Agudo (2017)
10.18632/oncotarget.24822
Endonuclease G promotes mitochondrial genome cleavage and replication
Rahel Stefanie Wiehe (2018)
10.1016/j.dnarep.2019.06.001
The Jekyll and Hyde character of RNase H1 and its multiple roles in mitochondrial DNA metabolism.
Ian J. Holt (2019)
10.1093/hmg/ddu336
Linear mtDNA fragments and unusual mtDNA rearrangements associated with pathological deficiency of MGME1 exonuclease
T. Nicholls (2014)
10.1186/s13059-020-02138-5
Ultrasensitive deletion detection links mitochondrial DNA replication, disease, and aging
S. Lujan (2020)
10.1007/978-1-4939-3040-1_5
A Single-Cell Resolution Imaging Protocol of Mitochondrial DNA Dynamics in Physiopathology, mTRIP, Which Also Evaluates Sublethal Cytotoxicity.
Laurent Châtre (2016)
Structure and biophysical studies of mitochondrial Transcription Factor A in complex with DNA
Anna Cuppari (2016)
Structural analysis of macromolecular nanomachines by 3d electron microscopy: managing flexibility and heterogenety in some define cases.
Álvarez Cabrera (2015)
Regulation of human mitochondrial gene expression
M. L. Sánchez (2014)
10.1186/s12862-020-01677-6
Potential causes and consequences of rapid mitochondrial genome evolution in thermoacidophilic Galdieria (Rhodophyta)
C. H. Cho (2020)
10.1016/j.mito.2018.01.004
Tissue specific differences in mitochondrial DNA maintenance and expression.
Elena Herbers (2019)
10.1016/j.mito.2014.05.009
GC skew and mitochondrial origins of replication.
Abdullah H. Sahyoun (2014)
10.12688/f1000research.21490.1
Recent advances in understanding mitochondrial genome diversity
Rafael Zardoya (2020)
10.1016/bs.enz.2016.03.006
Animal Mitochondrial DNA Replication.
G. Ciesielski (2016)
10.1093/mutage/gew058
Underlying role of mitochondrial mutagenesis in the pathogenesis of a disease and current approaches for translational research
M. Paraskevaidi (2017)
10.1007/s12010-018-2913-1
In Vitro Wound Healing Activity of Wheat-Derived Nanovesicles
Fikrettin Şahin (2018)
10.1042/EBC20170100
Mitochondrial DNA replication in mammalian cells: overview of the pathway
M. Falkenberg (2018)
10.1042/BST20160162
Mitochondrial DNA replication: a PrimPol perspective
L. Bailey (2017)
10.1038/nsmb.2957
Tracking replication enzymology in vivo by genome-wide mapping of ribonucleotide incorporation
A. R. Clausen (2015)
10.1016/j.ajhg.2015.05.013
RNASEH1 Mutations Impair mtDNA Replication and Cause Adult-Onset Mitochondrial Encephalomyopathy.
A. Reyes (2015)
10.1038/s41598-019-41464-y
G-quadruplex dynamics contribute to regulation of mitochondrial gene expression
M. Falabella (2019)
Molecular insights into mitochondrial transcription and its role in DNA replication
Viktor Posse (2016)
Developing mitoribosomal profiling to investigate quality control of human mitrochondrial protein synthesis
M. Wesołowska (2015)
10.1134/S0006297915110036
Mitochondrial matrix processes
I. Mazunin (2015)
10.1101/2020.09.10.291369
In vivo and in vitro mechanistic characterization of a clinically relevant PolγA mutation
Pedro Silva-Pinheiro (2020)
10.1002/bies.201400052
Unique features of DNA replication in mitochondria: A functional and evolutionary perspective
I. Holt (2014)
10.1371/journal.pgen.1004985
A Rolling Circle Replication Mechanism Produces Multimeric Lariats of Mitochondrial DNA in Caenorhabditis elegans
S. C. Lewis (2015)
10.1371/journal.pgen.1005779
MPV17 Loss Causes Deoxynucleotide Insufficiency and Slow DNA Replication in Mitochondria
I. Dalla Rosa (2016)
10.1093/nar/gky852
Transcript availability dictates the balance between strand-asynchronous and strand-coupled mitochondrial DNA replication
Tricia J. Cluett (2018)
10.1038/s41598-019-45244-6
Replication fork rescue in mammalian mitochondria
R. Torregrosa-Muñumer (2019)
10.1016/j.ijbiomac.2019.11.204
Double control regions of some flatfish mitogenomes evolve in a concerted manner.
Wei Shi (2019)
See more
Semantic Scholar Logo Some data provided by SemanticScholar