scholarly journals Mitochondrial DNA replication in mammalian cells: overview of the pathway

2018 ◽  
Vol 62 (3) ◽  
pp. 287-296 ◽  
Author(s):  
Maria Falkenberg
Keyword(s):  
Dna Replication ◽  
Mammalian Cells ◽  
Mitochondrial Diseases ◽  
Replication Machinery ◽  
Replication Process ◽  
Double Stranded Dna ◽  
Mammalian Mitochondria ◽  
Multiple Copies ◽  
Mitochondrial Replication ◽  
Replication Factors

Mammalian mitochondria contain multiple copies of a circular, double-stranded DNA genome and a dedicated DNA replication machinery is required for its maintenance. Many disease-causing mutations affect mitochondrial replication factors and a detailed understanding of the replication process may help to explain the pathogenic mechanisms underlying a number of mitochondrial diseases. We here give a brief overview of DNA replication in mammalian mitochondria, describing our current understanding of this process and some unanswered questions remaining.

Biochemical properties of mammalian TREX1 and its association with DNA replication and inherited inflammatory disease

2009 ◽  
Vol 37 (3) ◽  
pp. 535-538 ◽  
Author(s):  
Tomas Lindahl ◽  
Deborah E. Barnes ◽  
Yun-Gui Yang ◽  
Peter Robins
Keyword(s):  
Dna Replication ◽  
Lupus Erythematosus ◽  
Mammalian Cells ◽  
Genotoxic Stress ◽  
Biochemical Properties ◽  
Ataxia Telangiectasia Mutated ◽  
Checkpoint Activation ◽  
Familial Chilblain Lupus ◽  
Double Stranded Dna ◽  
Exonuclease 1

The major DNA-specific 3′–5′ exonuclease of mammalian cells is TREX1 (3′ repair exonuclease 1; previously called DNase III). The human enzyme is encoded by a single exon and, like many 3′ exonucleases, exists as a homodimer. TREX1 degrades ssDNA (single-stranded DNA) more efficiently than dsDNA (double-stranded DNA), and its catalytic properties are similar to those of Escherichia coli exonuclease X. However, TREX1 is only found in mammals and has an extended C-terminal domain containing a leucine-rich sequence required for its association with the endoplasmic reticulum. In normal S-phase and also in response to genotoxic stress, TREX1 at least partly redistributes to the cell nucleus. In a collaborative project, we have demonstrated TREX1 enzyme deficiency in Aicardi–Goutières syndrome. Subsequently, we have shown that AGS1 cells exhibit chronic ATM (ataxia telangiectasia mutated)-dependent checkpoint activation, and these TREX1-deficient cells accumulate ssDNA fragments of a distinct size generated during DNA replication. Other groups have shown that the syndromes of familial chilblain lupus as well as systemic lupus erythematosus, and the distinct neurovascular disorder retinal vasculopathy with cerebral leukodystrophy, can be caused by dominant mutations at different sites within the TREX1 gene.

scholarly journals DNA Replication in the Archaea

2006 ◽  
Vol 70 (4) ◽  
pp. 876-887 ◽  
Author(s):  
Elizabeth R. Barry ◽  
Stephen D. Bell
Keyword(s):  
Dna Replication ◽  
Higher Order ◽  
Striking Similarity ◽  
Replication Proteins ◽  
Replication Machinery ◽  
Replication Factors ◽  
Archaeal Dna Replication ◽  
Made In

SUMMARY The archaeal DNA replication machinery bears striking similarity to that of eukaryotes and is clearly distinct from the bacterial apparatus. In recent years, considerable advances have been made in understanding the biochemistry of the archaeal replication proteins. Furthermore, a number of structures have now been obtained for individual components and higher-order assemblies of archaeal replication factors, yielding important insights into the mechanisms of DNA replication in both archaea and eukaryotes.

scholarly journals Rolling-Circle Replication of an Animal Circovirus Genome in a Theta-Replicating Bacterial Plasmid in Escherichia coli

2006 ◽  
Vol 80 (17) ◽  
pp. 8686-8694 ◽  
Author(s):  
Andrew K. Cheung
Keyword(s):  
Escherichia Coli ◽  
Dna Replication ◽  
Mammalian Cells ◽  
Unit Length ◽  
Release Mechanism ◽  
Rolling Circle Replication ◽  
Replication Process ◽  
Rolling Circle ◽  
Rep Protein ◽  
Bacterial Plasmid

ABSTRACT A bacterial plasmid containing 1.75 copies of double-stranded porcine circovirus (PCV) DNA in tandem (0.8 copy of PCV type 1 [PCV1], 0.95 copy of PCV2) with two origins of DNA replication (Ori) yielded three different DNA species when transformed into Escherichia coli: the input construct, a unit-length chimeric PCV1Rep/PCV2Cap genome with a composite Ori but lacking the plasmid vector, and a molecule consisting of the remaining 0.75 copy PCV1Cap/PCV2Rep genome with a different composite Ori together with the bacterial plasmid. Replication of the input construct was presumably via the theta replication mechanism utilizing the ColE1 Ori, while characteristics of the other two DNA species, including a requirement of two PCV Oris and the virus-encoded replication initiator Rep protein, suggest they were generated via the rolling-circle copy-release mechanism. Interestingly, the PCV-encoded Rep′ protein essential for PCV DNA replication in mammalian cells was not required in bacteria. The fact that the Rep′ protein function(s) can be compensated by the bacterial replication machinery to support the PCV DNA replication process echoes previous suggestions that circular single-stranded DNA animal circoviruses, plant geminiviruses, and nanoviruses may have evolved from prokaryotic episomal replicons.

scholarly journals Electrical induction hypothesis to explain enhancer-promoter communication

2015 ◽  
Author(s):  
Valentina Agoni
Keyword(s):  
Transcription Factors ◽  
Dna Replication ◽  
Induction Hypothesis ◽  
Unsolved Problem ◽  
Specific Binding ◽  
Replication Machinery ◽  
Replication Process ◽  
Electrical Induction ◽  
Binding Sequence

The steps of the DNA replication process remains to be clarified. Transcription factors are supposed to find their specific binding-sequence driven by epigenetic modifications and GpC islands. But then how can the replication machinery be able to find the promoters of exactly the genes that the cell needs to transcribe in that moment? Here we hypothesize a role of DNA conductance and electrical induction to give an explanation to this unsolved problem. Our hypothesis goes in accordance with the fact that many authors identified 3D loops in the genomes.

scholarly journals Dynamic targeting of the replication machinery to sites of DNA damage

2004 ◽  
Vol 166 (4) ◽  
pp. 455-463 ◽  
Author(s):  
David A. Solomon ◽  
M. Cristina Cardoso ◽  
Erik S. Knudsen
Keyword(s):  
Dna Damage ◽  
Dna Replication ◽  
Nuclear Antigen ◽  
Replication Machinery ◽  
Dependent Protein ◽  
Specific Proteins ◽  
Turn Over ◽  
Dynamic Exchange ◽  
Replication Factors ◽  
Proliferating Cell

Components of the DNA replication machinery localize into discrete subnuclear foci after DNA damage, where they play requisite functions in repair processes. Here, we find that the replication factors proliferating cell nuclear antigen (PCNA) and RPAp34 dynamically exchange at these repair foci with discrete kinetics, and this behavior is distinct from kinetics during DNA replication. Posttranslational modification is hypothesized to target specific proteins for repair, and we find that accumulation and stability of PCNA at sites of damage requires monoubiquitination. Contrary to the popular notion that phosphorylation on the NH2 terminus of RPAp34 directs the protein for repair, we demonstrate that phosphorylation by DNA-dependent protein kinase enhances RPAp34 turnover at repair foci. Together, these findings support a dynamic exchange model in which multiple repair factors regulated by specific modifications have access to and rapidly turn over at sites of DNA damage.

scholarly journals How MCM loading and spreading specify eukaryotic DNA replication initiation sites

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2063 ◽  
Author(s):  
Olivier Hyrien
Keyword(s):  
Dna Replication ◽  
Mammalian Cells ◽  
Origin Recognition Complex ◽  
Cell Types ◽  
S Phase ◽  
Replication Initiation ◽  
Replication Process ◽  
Dna Replication Initiation ◽  
Eukaryotic Dna ◽  
Transcription Complexes

DNA replication origins strikingly differ between eukaryotic species and cell types. Origins are localized and can be highly efficient in budding yeast, are randomly located in early fly and frog embryos, which do not transcribe their genomes, and are clustered in broad (10-100 kb) non-transcribed zones, frequently abutting transcribed genes, in mammalian cells. Nonetheless, in all cases, origins are established during the G1-phase of the cell cycle by the loading of double hexamers of the Mcm 2-7 proteins (MCM DHs), the core of the replicative helicase. MCM DH activation in S-phase leads to origin unwinding, polymerase recruitment, and initiation of bidirectional DNA synthesis. Although MCM DHs are initially loaded at sites defined by the binding of the origin recognition complex (ORC), they ultimately bind chromatin in much greater numbers than ORC and only a fraction are activated in any one S-phase. Data suggest that the multiplicity and functional redundancy of MCM DHs provide robustness to the replication process and affect replication time and that MCM DHs can slide along the DNA and spread over large distances around the ORC. Recent studies further show that MCM DHs are displaced along the DNA by collision with transcription complexes but remain functional for initiation after displacement. Therefore, eukaryotic DNA replication relies on intrinsically mobile and flexible origins, a strategy fundamentally different from bacteria but conserved from yeast to human. These properties of MCM DHs likely contribute to the establishment of broad, intergenic replication initiation zones in higher eukaryotes.

scholarly journals Electrical induction hypothesis to explain enhancer-promoter communication

2015 ◽  
Author(s):  
Valentina Agoni
Keyword(s):  
Transcription Factors ◽  
Dna Replication ◽  
Induction Hypothesis ◽  
Unsolved Problem ◽  
Specific Binding ◽  
Replication Machinery ◽  
Replication Process ◽  
Electrical Induction ◽  
Binding Sequence

The steps of the DNA replication process remains to be clarified. Transcription factors are supposed to find their specific binding-sequence driven by epigenetic modifications and GpC islands. But then how can the replication machinery be able to find the promoters of exactly the genes that the cell needs to transcribe in that moment? Here we hypothesize a role of DNA conductance and electrical induction to give an explanation to this unsolved problem. Our hypothesis goes in accordance with the fact that many authors identified 3D loops in the genomes.

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