scholarly journals Extrachromosomal Circular DNAs: Origin, formation and emerging function in Cancer

2021 ◽  
Vol 17 (4) ◽  
pp. 1010-1025
Author(s):  
Man Wang ◽  
Xinzhe Chen ◽  
Fei Yu ◽  
Han Ding ◽  
Yuan Zhang ◽  
...  
Keyword(s):  
Circular Dnas

scholarly journals The Effect of Genomic DNA Contamination on the Detection of Circulating Long Non-Coding RNAs: The Paradigm of MALAT1

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1160
Author(s):  
Athina N. Markou ◽  
Stavroula Smilkou ◽  
Emilia Tsaroucha ◽  
Evi Lianidou
Keyword(s):  
False Positive ◽  
Tissue Samples ◽  
Dna Contamination ◽  
Dnase Treatment ◽  
Circular Dnas ◽  
Non Coding Rnas ◽  
Nsclc Patients ◽  
Treatment Step ◽  
Primary Tissue ◽  
Positive Results

The presence of contaminating gDNA in RNA preparations is a frequent cause of false positives in RT-PCR-based analysis. However, in some cases, this cannot be avoided, especially when there are no exons–intron junctions in the lncRNA sequences. Due to the lack of exons in few of long noncoding RNAs (lncRNAs) and the lack of DNAse treatment step in most studies reported so far, serious questions are raised about the specificity of lncRNA detection and the potential of reporting false-positive results. We hypothesized that minute amounts of gDNA usually co-extracted with RNA could give false-positive signals since primers would specifically bind to gDNA due to the lack of junction. In the current study, we evaluated the effect of gDNA and other forms of DNA like extrachromosomal circular DNAs (eccDNAs) contamination and the importance of including a DNAse treatment step on lncRNAsexpression.As a model, we have chosen as one of the most widely studied lncRNAs in cancer namely MALAT1, which lacks exons. When we tested this hypothesis in plasma and primary tissue samples from NSCLC patients, our findings clearly indicated that results on MALAT1 expression are highly affected by the presence of DNA contamination and that the DNAse treatment step is absolutely necessary to avoid false positive results.

Structure of extrachromosomal circular DNAs generated by immunoglobulin light chain gene rearrangements

1991 ◽  
Vol 27 (1) ◽  
pp. 19-23 ◽  
Author(s):  
Toshiyasu Hirama ◽  
Sunao Takeshita ◽  
Yataroh Yoshida ◽  
Hideo Yamagishi
Keyword(s):  
Light Chain ◽  
Chain Gene ◽  
Gene Rearrangements ◽  
Immunoglobulin Light Chain ◽  
Light Chain Gene ◽  
Circular Dnas

scholarly journals Newly Identified Antibacterial Compounds Are Topoisomerase Poisons in African Trypanosomes

2009 ◽  
Vol 54 (2) ◽  
pp. 620-626 ◽  
Author(s):  
Sonya C. Tang ◽  
Theresa A. Shapiro
Keyword(s):  
Topoisomerase Ii ◽  
Protozoan Parasite ◽  
New Drugs ◽  
Chemical Library ◽  
African Trypanosomes ◽  
Topoisomerase Poisons ◽  
Type Ia ◽  
Library Screen ◽  
Circular Dnas ◽  
Current Therapies

ABSTRACT Human African trypanosomiasis, caused by the Trypanosoma brucei protozoan parasite, is fatal when left untreated. Current therapies are antiquated, and there is a need for new pharmacologic agents against T. brucei targets that have no human ortholog. Trypanosomes have a single mitochondrion with a unique mitochondrial DNA, known as kinetoplast DNA (kDNA), a topologically complex network that contains thousands of interlocking circular DNAs, termed minicircles (∼1 kb) and maxicircles (∼23 kb). Replication of kDNA depends on topoisomerases, enzymes that catalyze reactions that change DNA topology. T. brucei has an unusual type IA topoisomerase that is dedicated to kDNA metabolism. This enzyme has no ortholog in humans, and RNA interference (RNAi) studies have shown that it is essential for parasite survival, making it an ideal drug target. In a large chemical library screen, two compounds were recently identified as poisons of bacterial topoisomerase IA. We found that these compounds are trypanocidal in the low micromolar range and that they promote the formation of linearized minicircles covalently bound to protein on the 5′ end, consistent with the poisoning of mitochondrial topoisomerase IA. Surprisingly, however, band depletion studies showed that it is topoisomerase IImt, and not topoisomerase IAmt, that is trapped. Both compounds are planar aromatic polycyclic structures that intercalate into and unwind DNA. These findings reinforce the utility of topoisomerase IImt as a target for development of new drugs for African sleeping sickness.

442 — Polarography of circular DNAs

1981 ◽  
Vol 8 (5) ◽  
pp. 487-496 ◽  
Author(s):  
M. Vojtíšková ◽  
E. Lukášová ◽  
F. Jelen ◽  
E. Paleček
Keyword(s):  
Circular Dnas

Characterization of mutant mitochondrial plasmids of Neurospora spp. that have incorporated tRNAs by reverse transcription

1989 ◽  
Vol 9 (2) ◽  
pp. 678-691
Author(s):  
R A Akins ◽  
R L Kelley ◽  
A M Lambowitz
Keyword(s):  
Mitochondrial Dna ◽  
Reverse Transcription ◽  
Transcription Initiation ◽  
Consensus Sequence ◽  
Trna Genes ◽  
Wild Type ◽  
Mitochondrial Trna ◽  
Mitochondrial Plasmids ◽  
Circular Dnas ◽  
Mitochondrial Introns

The Mauriceville and Varkud mitochondrial plasmids of Neurospora spp. are closely related, closed-circular DNAs (3.6 and 3.7 kilobases, respectively) whose nucleotide sequences and genetic organization suggest relationships to mitochondrial introns and retroelements. We have characterized nine suppressive mutants of these plasmids that outcompete mitochondrial DNA and lead to impaired growth. All nine suppressive plasmids contain small insertions, corresponding to or including a mitochondrial tRNA (tRNATrp, tRNAGly, or tRNAVal) or a tRNA-like sequence. The insertions are located at the position corresponding to the 5' end of the major plasmid transcript or 24 nucleotides downstream near a cognate of the sequence at the major 5' RNA end. The structure of the suppressive plasmids suggests that the tRNAs were inserted via an RNA intermediate. The 3' end of the wild-type plasmid transcript can itself be folded into a secondary structure which has tRNA-like characteristics, similar to the tRNA-like structures at the 3' ends of plant viral RNAs. This structure may play a role in replication of the plasmids by reverse transcription. Major transcripts of the suppressive plasmids begin at the 5' end of the inserted mitochondrial tRNA sequence and are present in 25- to 100-fold-higher concentrations than are transcripts of wild-type plasmids. Mapping of 5' RNA ends within the inserted mtDNA sequences identifies a short consensus sequence (PuNPuAG) which is present at the 5' ends of a subset of mitochondrial tRNA genes. This sequence, together with sequences immediately upstream in the plasmids, forms a longer consensus sequence, which is similar to sequences at transcription initiation sites in Neurospora mitochondrial DNA. The suppressive behavior of the plasmids is likely to be directly related to the insertion of tRNAs leading to overproduction of plasmid transcripts.

A mitochondrial retroplasmid integrates into mitochondrial DNA by a novel mechanism involving the synthesis of a hybrid cDNA and homologous recombination

1994 ◽  
Vol 14 (10) ◽  
pp. 6419-6432
Author(s):  
C C Chiang ◽  
J C Kennell ◽  
L A Wanner ◽  
A M Lambowitz
Keyword(s):  
Mitochondrial Dna ◽  
Homologous Recombination ◽  
Rrna Gene ◽  
Template Switching ◽  
Transcript Analysis ◽  
Wild Type ◽  
Mitochondrial Trna ◽  
Integration Mechanism ◽  
Circular Dnas ◽  
Simple Integration

The Mauriceville and Varkud mitochondrial plasmids of Neurospora spp. are closely related, small circular DNAs that propagate via an RNA intermediate and reverse transcription. Although the plasmids ordinarily replicate autonomously, they can also integrate into mitochondrial DNA (mtDNA), yielding defective mtDNAs that in some cases cause senescence. To investigate the integration mechanism, we analyzed four cases in which the Varkud plasmid integrated into the mitochondrial small rRNA gene, three in wild-type subcultures and one in a senescent mutant. Our analysis suggests that the integrations occurred by the plasmid reverse transcriptase template switching between the plasmid transcript and internal sequences in the mitochondrial small rRNA to yield hybrid cDNAs that circularized and recombined homologously with the mtDNA. The integrated plasmid sequences are transcribed, presumably from the mitochondrial small rRNA promoters, resulting in hybrid RNAs containing the 5' segment of the mitochondrial small rRNA linked head-to-tail to the full-length plasmid transcript. Analysis of additional senescent mutants revealed three cases in which the plasmid used the same mechanism to integrate at other locations in the mtDNA. In these cases, circular variant plasmids that had incorporated a mitochondrial tRNA or tRNA-like sequence by template switching integrated by homologous recombination at the site of the corresponding tRNA or tRNA-like sequence in mtDNA. This simple integration mechanism involving template switching to generate a hybrid cDNA that integrates homologously could have been used by primitive retroelements prior to the acquisition of a specialized integration machinery.

scholarly journals Transposable elements and circular DNAs

2016 ◽  
Vol 6 (6) ◽  
pp. e1240748 ◽  
Author(s):  
Tobias Mourier
Keyword(s):  
Transposable Elements ◽  
Circular Dnas

scholarly journals Robust HIV-1 replication in the absence of integrase function

2020 ◽  
Author(s):  
Ishak D. Irwan ◽  
Heather L. Karnowski ◽  
Hal P. Bogerd ◽  
Kevin Tsai ◽  
Bryan R. Cullen
Keyword(s):  
Transcription Factor ◽  
Leukemia Virus ◽  
Epigenetic Silencing ◽  
Epigenetic Marks ◽  
Proviral Dna ◽  
Human T Cell ◽  
T Cell Leukemia Virus ◽  
Circular Dnas ◽  
Episomal Dna ◽  
Hiv 1

AbstractIntegration of the proviral DNA intermediate into the host cell genome represents an essential step in the retroviral life cycle. While the reason(s) for this requirement remains unclear, it is known that unintegrated proviral DNA is epigenetically silenced. Here, we demonstrate that HIV-1 mutants lacking functional integrase can mount a robust, spreading infection in cells expressing the Tax transcription factor encoded by human T-cell leukemia virus 1. In these cells, HIV-1 forms episomal DNA circles, analogous to Hepatitis B virus covalently closed circular DNAs (cccDNAs), that are transcriptionally active and fully capable of supporting viral replication. This rescue correlates with the loss of inhibitory epigenetic marks, and the acquisition of activating marks, on histones bound to unintegrated HIV-1 DNA. Thus retroviral DNA integration may have evolved, at least in part, as a mechanism to avoid the epigenetic silencing of extrachromosomal viral DNA by host innate antiviral factors.SignificanceWhile retroviral DNA is synthesized normally after infection by integrase-deficient viruses, the resultant episomal DNA is then epigenetically silenced. Here, we show that expression of the Tax transcription factor encoded by a second human retrovirus, HTLV-1, prevents the epigenetic silencing of unintegrated HIV-1 DNA and instead induces the addition of activating epigenetic marks, and the recruitment of NF-kB/Rel proteins, to the HIV-1 LTR promoter. Moreover, in the presence of Tax, the HIV-1 DNA circles that form in the absence of integrase function are not only efficiently transcribed but also support a spreading, pathogenic IN- HIV-1 infection. Thus, retroviruses have the potential to replicate without integration, as is indeed seen with HBV.

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