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In D-loop: 40years Of Mitochondrial 7S DNA

T. Nicholls, Michal Minczuk
Published 2014 · Biology, Medicine

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Given the tiny size of the mammalian mitochondrial genome, at only 16.5 kb, it is often surprising how little we know about some of its molecular features, and the molecular mechanisms governing its maintenance. One such conundrum is the biogenesis and function of the mitochondrial displacement loop (D-loop). The mitochondrial D-loop is a triple-stranded region found in the major non-coding region (NCR) of many mitochondrial genomes, and is formed by stable incorporation of a third, short DNA strand known as 7S DNA. In this article we review the current affairs regarding the main features of the D-loop structure, the diverse frequency of D-loops in the mtDNAs of various species and tissues, and also the mechanisms of its synthesis and turnover. This is followed by an account of the possible functions of the mitochondrial D-loop that have been proposed over the last four decades. In the last section, we discuss the potential links of the D-loop with mammalian ageing.
This paper references
10.1128/MCB.10.11.5671
Mitochondrial DNA structure and expression in specialized subtypes of mammalian striated muscle.
B. Annex (1990)
10.1093/nar/gkq493
Differential regulation of full-length genome and a single-stranded 7S DNA along the cell cycle in human mitochondria
Anita Antes (2010)
10.1074/jbc.272.24.15275
In Vivo Determination of Replication Origins of Human Mitochondrial DNA by Ligation-mediated Polymerase Chain Reaction*
D. Kang (1997)
10.1093/NAR/27.11.2434
Cell-by-cell scanning of whole mitochondrial genomes in aged human heart reveals a significant fraction of myocytes with clonally expanded deletions.
K. Khrapko (1999)
10.1016/0022-2836(78)90269-3
Mechanism of mitochondrial DNA replication in mouse L-cells: kinetics of synthesis and turnover of the initiation sequence.
D. Bogenhagen (1978)
10.1016/j.bbamcr.2010.04.008
Mitochondrial single-stranded DNA binding protein is required for maintenance of mitochondrial DNA and 7S DNA but is not required for mitochondrial nucleoid organisation.
Heini Ruhanen (2010)
10.1074/jbc.M109.016600
Human Heart Mitochondrial DNA Is Organized in Complex Catenated Networks Containing Abundant Four-way Junctions and Replication Forks*
J. Pohjoismäki (2009)
10.1016/J.MITO.2007.06.004
Mammalian mitochondrial nucleoids: organizing an independently minded genome.
I. Holt (2007)
10.1021/bi800774b
Mitochondrial topoisomerase I sites in the regulatory D-loop region of mitochondrial DNA.
H. Zhang (2008)
10.1093/hmg/ddt051
TWINKLE is an essential mitochondrial helicase required for synthesis of nascent D-loop strands and complete mtDNA replication
D. Milenkovic (2013)
Loss-of-function mutations inMGME1 impairmtDNA replication and causemultisystemicmitochondrial disease
C. Kornblum (2013)
10.1016/0022-2836(81)90454-X
A small polyadenylated RNA (7 S RNA), containing a putative ribosome attachment site, maps near the origin of human mitochondrial DNA replication.
D. Ojala (1981)
10.1073/pnas.69.12.3810
Replication of mitochondrial DNA in mouse L cells and their thymidine kinase - derivatives: displacement replication on a covalently-closed circular template.
D. Robberson (1972)
10.1371/journal.pbio.0060010
Strong Purifying Selection in Transmission of Mammalian Mitochondrial DNA
J. B. Stewart (2008)
10.1016/S0197-4580(02)00233-6
High mutational burden in the mtDNA control region from aged muscles: a single-fiber study
R. Bo (2003)
10.1083/jcb.200609158
The AAA+ protein ATAD3 has displacement loop binding properties and is involved in mitochondrial nucleoid organization
J. He (2007)
10.1093/nar/gkt029
Identification of a novel human mitochondrial endo-/exonuclease Ddk1/c20orf72 necessary for maintenance of proper 7S DNA levels
Roman J Szczesny (2013)
10.1093/NAR/29.17.3657
Mechanism of mammalian mitochondrial DNA replication: import of mitochondrial transcription factor A into isolated mitochondria stimulates 7S DNA synthesis.
S. Gensler (2001)
10.1073/pnas.75.2.735
Human mitochondrial DNA: analysis of 7S DNA from the origin of replication.
W. Brown (1978)
10.1093/nar/gkp091
Mice expressing an error-prone DNA polymerase in mitochondria display elevated replication pausing and chromosomal breakage at fragile sites of mitochondrial DNA
L. Bailey (2009)
10.1016/0014-4827(91)90467-9
Organization of multiple nucleoids and DNA molecules in mitochondria of a human cell.
M. Satoh (1991)
10.1073/pnas.68.9.2252
A novel closed-circular mitochondrial DNA with properties of a replicating intermediate.
H. Kasamatsu (1971)
10.1038/sj.emboj.7601392
Replication of vertebrate mitochondrial DNA entails transient ribonucleotide incorporation throughout the lagging strand
T. Yasukawa (2006)
10.1038/277192a0
Nucleotide sequence of a region of human mitochondrial DNA containing the precisely identified origin of replication
S. Crews (1979)
10.1093/nar/gkp348
Intra- and inter-molecular recombination of mitochondrial DNA after in vivo induction of multiple double-strand breaks
S. Bacman (2009)
Regulation of mitochondrial D-loops by transcription factor A and single-stranded DNA-binding protein
高松 千洋 (2002)
10.1016/0005-2787(71)90147-X
The presence of DNA molecules with a displacement loop in standard mitochondrial DNA preparations.
A. Arnberg (1971)
10.1073/pnas.74.4.1348
Association of a protein structure of probable membrane derivation with HeLa cell mitochondrial DNA near its origin of replication.
M. Albring (1977)
10.1126/SCIENCE.286.5440.774
Aging-dependent large accumulation of point mutations in the human mtDNA control region for replication.
Y. Michikawa (1999)
10.1073/pnas.69.3.737
Replication of mitochondrial DNA. Circular replicative intermediates in mouse L cells.
D. Robberson (1972)
10.1016/0092-8674(92)90528-K
Evidence against a mitochondrial location of the 7-2/MRP RNA in mammalian cells
T. Kiss (1992)
10.2210/pdb3tmm/pdb
TFAM imposes a U-turn on mitochondrial DNA
Huu B. Ngo (2011)
10.1007/s10863-010-9269-8
Topological analysis of ATAD3A insertion in purified human mitochondria
Arnaud Hubstenberger (2010)
10.1073/PNAS.94.25.13798
Mitochondrial mutational spectra in human cells and tissues.
K. Khrapko (1997)
10.1073/pnas.0630589100
Control region mtDNA variants: Longevity, climatic adaptation, and a forensic conundrum
P. Coskun (2003)
10.1073/pnas.1006026107
G-quadruplex structures in RNA stimulate mitochondrial transcription termination and primer formation
P. Wanrooij (2010)
10.1016/j.exger.2011.01.003
Absence of association between mitochondrial DNA C150T polymorphism and longevity in a Han Chinese population
H. Pan (2011)
10.1128/MCB.13.4.2162
Protein binding to a single termination-associated sequence in the mitochondrial DNA D-loop region.
C. S. Madsen (1993)
10.1093/nar/gks802
A hybrid G-quadruplex structure formed between RNA and DNA explains the extraordinary stability of the mitochondrial R-loop
P. Wanrooij (2012)
10.1016/0092-8674(82)90049-6
Replication of animal mitochondrial DNA
D. Clayton (1982)
10.1016/j.cell.2008.06.016
A Mitochondrial Protein Compendium Elucidates Complex I Disease Biology
D. J. Pagliarini (2008)
10.1038/ng.2501
Loss-of-function mutations in MGME1 impair mtDNA replication and cause multisystemic mitochondrial disease
C. Kornblum (2013)
10.1007/BF02100199
The main regulatory region of mammalian mitochondrial DNA: Structure-function model and evolutionary pattern
C. Saccone (2005)
In vitro replication of mitochondrial DNA. Elongation of the endogenous primer sequence in D loop mitochondrial DNA by human DNA polymerase beta.
D. Eichler (1977)
10.1016/0014-4827(83)90114-3
Changes in D-loop frequency and superhelicity among the mitochondrial DNA molecules in relation to organelle biogenesis in oocytes of Xenopus laevis.
J. Callen (1983)
10.1093/NAR/30.9.2004
Release of replication termination controls mitochondrial DNA copy number after depletion with 2',3'-dideoxycytidine.
T. Brown (2002)
10.1146/annurev-biochem-060408-093701
Somatic mitochondrial DNA mutations in mammalian aging.
N. Larsson (2010)
10.1016/j.tcb.2013.04.009
mtDNA makes a U-turn for the mitochondrial nucleoid.
Christian Kukat (2013)
DNA in Xenopus laevis oocytes I
R. L. Hallberg (1974)
10.1038/13779
Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA
R. M. Andrews (1999)
10.1073/pnas.061013598
Muscle-specific mutations accumulate with aging in critical human mtDNA control sites for replication
Y. Wang (2001)
10.1126/SCIENCE.1096342
Recombination of Human Mitochondrial DNA
Y. Kraytsberg (2004)
Pulse-labeled components in the replication of mitochondrial deoxyribonucleic acid.
D. Robberson (1973)
10.1126/SCIENCE.1102077
Discovery of a Major D-Loop Replication Origin Reveals Two Modes of Human mtDNA Synthesis
J. Fish (2004)
10.1038/339309a0
An autosomal dominant disorder with multiple deletions of mitochondrial DNA starting at the D-loop region
M. Zeviani (1989)
10.1073/pnas.82.2.351
Priming of human mitochondrial DNA replication occurs at the light-strand promoter.
D. D. Chang (1985)
10.1073/pnas.78.10.6116
Elongation of displacement-loop strands in human and mouse mitochondrial DNA is arrested near specific template sequences.
J. N. Doda (1981)
10.1002/j.1460-2075.1992.tb05459.x
7‐2/MRP RNAs in plant and mammalian cells: association with higher order structures in the nucleolus.
Tamás Gábor Kiss (1992)
10.1006/BBRC.1997.8052
Multiple protein-binding sites in the TAS-region of human and rat mitochondrial DNA.
M. Roberti (1998)
10.1128/MCB.05694-11
Superresolution Fluorescence Imaging of Mitochondrial Nucleoids Reveals Their Spatial Range, Limits, and Membrane Interaction
T. Brown (2011)
10.1074/jbc.M602429200
Conserved Sequence Box II Directs Transcription Termination and Primer Formation in Mitochondria*
X. H. Pham (2006)
10.1126/science.2035027
Similarity of human mitochondrial transcription factor 1 to high mobility group proteins.
M. Parisi (1991)
10.1093/NAR/GKM676
The mitochondrial transcription termination factor mTERF modulates replication pausing in human mitochondrial DNA
Anne K. Hyvärinen (2007)
10.1038/nature02517
Premature ageing in mice expressing defective mitochondrial DNA polymerase
A. Trifunović (2004)
10.1038/290457a0
Sequence and organization of the human mitochondrial genome
S. Anderson (1981)
10.1016/0014-5793(94)01063-3
Ageing‐associated tandem duplications in the D‐loop of mitochondrial DNA of human muscle
H. Lee (1994)
10.1074/jbc.M806174200
Native R-loops Persist throughout the Mouse Mitochondrial DNA Genome*S⃞
T. Brown (2008)
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)
10.1016/0012-1606(74)90012-8
Mitochondrial DNA in Xenopus laevis oocytes. I. Displacement loop occurrence.
R. Hallberg (1974)
10.1016/S0378-1119(97)00404-6
Mammalian mitochondrial D-loop region structural analysis: identification of new conserved sequences and their functional and evolutionary implications.
E. Sbisà (1997)
10.1093/nar/gkp614
The accessory subunit of mitochondrial DNA polymerase γ determines the DNA content of mitochondrial nucleoids in human cultured cells
M. Di Re (2009)
10.1111/j.1365-2958.2009.06909.x
Replication fork collisions cause pathological chromosomal amplification in cells lacking RecG DNA translocase
Christian J Rudolph (2009)
10.1002/j.1460-2075.1985.tb03817.x
Replication priming and transcription initiate from precisely the same site in mouse mitochondrial DNA.
D. D. Chang (1985)
10.1073/pnas.75.8.3886
Origin and direction of replication in mitochondrial DNA molecules from Drosophila melanogaster.
J. Goddard (1978)
10.1101/GAD.11.5.582
RNase mitochondrial RNA processing correctly cleaves a novel R loop at the mitochondrial DNA leading-strand origin of replication.
D. Y. Lee (1997)
10.1016/0022-2836(74)90355-6
Mechanism of mitochondrial DNA replication in mouse L-cells: asynchronous replication of strands, segregation of circular daughter molecules, aspects of topology and turnover of an initiation sequence.
A. Berk (1974)
10.1093/nar/9.20.5411
Sequence and properties of the human KB cell and mouse L cell D-loop regions of mitochondrial DNA.
M. W. Walberg (1981)
10.1016/j.cell.2011.06.051
The Human Mitochondrial Transcriptome
T. Mercer (2011)
10.1038/nsmb.2160
Human mitochondrial transcription factor A induces a U-turn structure in the light strand promoter
A. Rubio-Cosials (2011)
10.1016/S0022-510X(02)00247-2
Evidence and age-related distribution of mtDNA D-loop point mutations in skeletal muscle from healthy subjects and mitochondrial patients
R. Bo (2002)
10.1038/nature12312
Avoiding chromosome pathology when replication forks collide
Christian J Rudolph (2013)
10.1074/jbc.M207030200
DNA Binding Properties of Human pol γB*
J. Carrodeguas (2002)
10.1016/0092-8674(77)90123-4
The mitochondrial DNA of drosophila melanogaster exists in two distinct and stable superhelical forms
J. Rubenstein (1977)
10.1002/j.1460-2075.1987.tb04770.x
A novel endoribonuclease cleaves at a priming site of mouse mitochondrial DNA replication.
D. D. Chang (1987)
10.1093/embo-reports/kve233
Prominent mitochondrial DNA recombination intermediates in human heart muscle
O. Kajander (2001)
10.1002/j.1460-2075.1996.tb00676.x
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.
B. Xu (1996)



This paper is referenced by
10.1093/nar/gkz277
The mitochondrial R-loop
I. Holt (2019)
10.1093/humupd/dmx018
Novel reproductive technologies to prevent mitochondrial disease
L. Craven (2017)
The source and fate of mitochondrial DNA mutations using high-sensitivity next-generation sequencing technologies
Marita A Isokallio (2017)
10.1101/706093
Precise annotation of human, chimpanzee, rhesus macaque and mouse mitochondrial genomes using 5’ and 3’ end small RNAs
Zhi Cheng (2019)
10.1371/journal.pone.0168283
Therapeutic Targeting of the Mitochondria Initiates Excessive Superoxide Production and Mitochondrial Depolarization Causing Decreased mtDNA Integrity
Kaytee L. Pokrzywinski (2016)
10.1038/srep13571
Computational DNA hole spectroscopy: A new tool to predict mutation hotspots, critical base pairs, and disease ‘driver’ mutations
Martha Y. Suárez (2015)
10.3390/jcm8111983
Mitochondrial Dysfunction in Aging and Cancer
L. Moro (2019)
10.1016/B978-0-12-800040-3.00013-3
Mitochondrial Disorders Causing Cardioskeletal Myopathies in Childhood
Sirisak Chanprasert (2017)
10.1093/brain/awx295
Heterozygous SSBP1 start loss mutation co-segregates with hearing loss and the m.1555A>G mtDNA variant in a large multigenerational family
P. Kullar (2018)
10.1038/s41598-020-59631-x
The role of control region mitochondrial DNA mutations in cardiovascular disease: stroke and myocardial infarction
Miriam Umbria (2020)
10.1016/j.mrfmmm.2018.01.005
Replication stress in mitochondria.
M. Ricchetti (2018)
10.1146/annurev-biochem-060815-014402
Maintenance and Expression of Mammalian Mitochondrial DNA.
C. Gustafsson (2016)
10.1038/s41598-019-47570-1
Sharing of heteroplasmies between human liver lobes varies across the mtDNA genome
A. Hübner (2019)
10.1134/S0026893319010060
Termination of Replication and Mechanisms of Heteroplasmy in Sturgeon Mitochondrial DNA
I. Kornienko (2019)
10.1038/s41467-017-00377-y
Mitochondrial mutations drive prostate cancer aggression
J. Hopkins (2017)
10.1167/tvst.8.6.43
Epigenetic Modifications in Peripheral Blood as Potential Noninvasive Biomarker of Diabetic Retinopathy
A. J. Duraisamy (2019)
10.1101/155796
Sharing of heteroplasmies between human liver lobes varies across the mtDNA genome
Alexander Hübner (2018)
10.1007/978-981-13-8367-0_12
Advances Towards Therapeutic Approaches for mtDNA Disease.
I. Al Khatib (2019)
10.1002/advs.201800927
3D Cultures of Parkinson's Disease‐Specific Dopaminergic Neurons for High Content Phenotyping and Drug Testing
Silvia Bolognin (2019)
10.3390/ijms20194959
Replication Stress at Telomeric and Mitochondrial DNA: Common Origins and Consequences on Ageing
P. Billard (2019)
Functional Investigation of OXPHOS assembly factors in Leber’s Hereditary Optic Neuropathy
Maria Inês Arêlo Manso da Fonseca (2016)
10.1134/S0006297919080042
DNA Replication in Human Mitochondria
L. A. Zinovkina (2019)
10.1002/ana.24571
Mitochondrial DNA Depletion in Respiratory Chain–Deficient Parkinson Disease Neurons
A. Grünewald (2016)
10.1101/291435
The Mitochondrial DNA Control Region might have useful Diagnostic and Prognostic Biomarkers for Thyroid Tumors
Rifat Bircan (2018)
10.3389/fonc.2017.00262
The Landscape of mtDNA Modifications in Cancer: A Tale of Two Cities
Kate L. Hertweck (2017)
10.1101/155796
Mitochondrial DNA heteroplasmy is shared between human liver lobes
Manja Wachsmuth (2017)
10.1055/a-0869-7355
The Mitochondrial DNA Control Region Might Have Useful Diagnostic and Prognostic Biomarkers for Thyroid Tumors
Rıfat Bircan (2019)
10.1073/pnas.1811661116
Chloroplast competition is controlled by lipid biosynthesis in evening primroses
J. Sobanski (2019)
10.1161/JAHA.119.015197
Associations of Peripheral Artery Disease With Calf Skeletal Muscle Mitochondrial DNA Heteroplasmy.
M. Gonzalez-Freire (2020)
10.1038/s41598-020-70225-5
Forensic validation of a panel of 12 SNPs for identification of Mongolian wolf and dog
Hong Hui Jiang (2020)
10.1007/978-981-13-8367-0
Mitochondria in Health and in Sickness
A. Urbani (2019)
10.1007/978-3-030-41283-8_6
DNA Repair and Mutagenesis in Vertebrate Mitochondria: Evidence for Asymmetric DNA Strand Inheritance.
B. T. Matkarimov (2020)
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