The role of extracellular DNA (exDNA) in cellular processes

Fernández-Domínguez, Ileana J; Manzo-Merino, Joaquín; Taja‐Chayeb, Lucía; Dueñas‐González, Alfonso; Pérez-Cárdenas, Enrique; Trejo-Becerril, Catalina

doi:10.1080/15384047.2021.1890319

Cited by 15 publications

(15 citation statements)

References 134 publications

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“…Recently, cirDNA has been shown to participate in blood coagulation [88]. Evidence that supports this asseveration is that purified genomic DNA increases the activation of proteases that participate in the blood clotting pathway, such as the coagulation factors XII and XI.…”

Section: Role Of Cirdna In Angiogenesis and Blood Coagulationmentioning

confidence: 95%

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The Influence of Proteins on Fate and Biological Role of Circulating DNA

Tutanov

Тамкович

2022

IJMS

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Circulating DNA has already proven itself as a valuable tool in translational medicine. However, one of the overlooked areas of circulating DNA research is its association with different proteins, despite considerable evidence that this association might impact DNA’s fate in circulation and its biological role. In this review, we attempt to shed light on current ideas about circulating DNA origins and forms of circulation, known biological effects, and the clinical potential of circulating tumor deoxyribonucleoprotein complexes.

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Section: Role Of Cirdna In Angiogenesis and Blood Coagulationmentioning

confidence: 95%

“…Moreover, cirDNA from activated neutrophils that are part of the NETs trigger blood clotting that relies on FXII and FXI. Furthermore, it has been observed that histones interact with the A1 domain of the von Willebrand human factor, which can propagate platelet adhesion mediated by GPIbα [88].…”

Section: Role Of Cirdna In Angiogenesis and Blood Coagulationmentioning

confidence: 99%

The Influence of Proteins on Fate and Biological Role of Circulating DNA

Tutanov

Тамкович

2022

IJMS

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“…Longer cf-eccDNA fragments appears to carry higher methylation densities in plasma of both pregnant and non-pregnant subjects [176] . Furthermore, nuclease activity on cf-eccDNA was reported, showing that DNASE1L3 affected eccDNA characteristics [177] .…”

Section: "New" Components Of Cfdnamentioning

confidence: 99%

Expanded knowledge of cell-free DNA biology: potential to broaden the clinical utility

Che¹,

Stanley²,

Jatsenko³

et al. 2022

Extracell Vesicles Circ Nucleic Acids

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Noninvasive sampling of an individual’s body fluids is an easy means to capture circulating cell-free DNA (cfDNA). These small fragments of DNA carry information on the contributing cell’s genome, epigenome, and nuclease content. Analysis of cfDNA for the assessment of genetic risk has already revolutionized clinical practice, and a compendium of increasingly higher-resolution approaches based on epigenetic and fragmentomic cfDNA signatures continues to expand. Profiling cfDNA has unlocked a wealth of molecular information that can be translated to the clinic. This review covers the biological characteristics of cfDNA, recent advances in liquid biopsy and the clinical utility of cfDNA.

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“…Recently, c-cfDNA has been considered not only as a diagnostic marker but also a potential therapeutic target [ 27 , 28 , 29 , 30 ]. In vitro experiments have shown that the c-cfDNA of patients with cardiovascular and autoimmune diseases has a pronounced biological activity with respect to various types of human cells [ 9 , 31 , 32 , 33 ].…”

Section: Introductionmentioning

confidence: 99%

In Vitro Analysis of Biological Activity of Circulating Cell-Free DNA Isolated from Blood Plasma of Schizophrenic Patients and Healthy Controls

Ershova

Shmarina

Porokhovnik

et al. 2022

Genes

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Schizophrenia is associated with low-grade systemic inflammation. Circulating cell-free DNA (c-cfDNA) belongs to the DAMP class. The major research question was: can the c-cfDNA of schizophrenic patients (sz-cfDNA) stimulate the DNA sensor genes, which control the innate immunity? We investigated the in vitro response of ten human skin fibroblast (HSF) lines to five DNA probes containing different amounts of a GC-rich marker (the ribosomal repeat) and a DNA oxidation marker (8-oxodG) including sz-cfDNA and healthy control c-cfDNA (hc-cfDNA) probes. After 1 h, 3 h, and 24 h of incubation, the expression of 6 protein genes responsible for cfDNA transport into the cell (EEA1 and HMGB1) and the recognition of cytosolic DNA (TLR9, AIM2, STING and RIG-I) was analyzed at the transcriptional (RT-qPCR) and protein level (flow cytometry and fluorescence microscopy). Additionally, we analyzed changes in the RNA amount of 32 genes (RT-qPCR), which had been previously associated with different cellular responses to cell-free DNA with different characteristics. Adding sz-cfDNA and hc-cfDNA to the HSF medium in equal amounts (50 ng/mL) blocked endocytosis and stimulated TLR9 and STING gene expression while blocking RIG-I and AIM2 expression. Sz-cfDNA and hc-cfDNA, compared to gDNA, demonstrated much stronger stimulated transcription of genes that control cell proliferation, cytokine synthesis, apoptosis, autophagy, and mitochondrial biogenesis. No significant difference was observed in the response of the cells to sz-cfDNA and hc-cfDNA. Sz-cfDNA and hc-cfDNA showed similarly high biological activity towards HSFs, stimulating the gene activity of TLR9 and STING DNA sensor proteins and blocking the activity of the AIM2 protein gene. Since the sz-cfDNA content in the patients’ blood is several times higher than the hc-cfDNA content, sz-cfDNA may upregulate pro-inflammatory cytokines in schizophrenia.

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The role of extracellular DNA (exDNA) in cellular processes

Cited by 15 publications

References 134 publications

The Influence of Proteins on Fate and Biological Role of Circulating DNA

The Influence of Proteins on Fate and Biological Role of Circulating DNA

Expanded knowledge of cell-free DNA biology: potential to broaden the clinical utility

In Vitro Analysis of Biological Activity of Circulating Cell-Free DNA Isolated from Blood Plasma of Schizophrenic Patients and Healthy Controls

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