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Monocyte and lymphocyte membrane markers: Ontogeny and clinical significance
Published in Gabriel Virella, Medical Immunology, 2019
Scott Sugden, Damien Montamat-Sicotte, Karen K. Yam, Joseph Murphy, Bader Yassine Diab, Virginia Litwin
Signaling through the pre-TCR generates activation signals, which lead to a cascade of proliferation and differentiation, such as the co-expression of CD4 and CD8, characteristic of the double-positive thymocyte population. These cells re-express their RAG genes and undergo TCRα gene rearrangement. Rearrangement of the TCRα gene results in the deletion of the δ gene, which will appear as extrachromosomal circular DNA in germline configuration. Upon successful rearrangement of the VαJαCα chain, the pre-Tα chain of the pre-TCR is replaced by the newly synthesized α chain, and the TCR2 (αβ) with a full complement of CD3 molecules, is inserted in the T cell membrane (Figure 10.5).
Mobile DNA Sequences and Their Possible Role in Evolution
Published in S. K. Dutta, DNA Systematics, 2019
Georgii P. Georgiev, Yurii V. Ilyin, Alexei P. Ryskov, Tatiana I. Gerasimova
The mechanism of provirus insertion is more or less clear in the case of exogenous infection. RNA injected into the cell is reverse transcribed and the linear DNA copy with two LTR elements is formed in the cytoplasm. Afterward, it moves to the nucleus and is circularized. As a result, the extrachromosomal circular DNA with two or one LTR element is formed in the infected cells.27,76,77 This may be considered as an intermediate in the insertion process.
Reorganization of the Genome During Aging of Proliferative Cell Compartments
Published in Alvaro Macieira-Coelho, Molecular Basis of Aging, 2017
It is believed that during the division cycle circular DNA detaches and reintegrates again in the genome. It is possible that in the postmitotic cells the circles do not reintegrate into the chromosomes because of the profound chromatin structural reorganization. The presence of highly repeated sequences near the two alpha-globin genes, as well as in the vicinity of the actin genes and in circular molecules detected in terminal cells,54 suggests a mechanism by which these circles could be recovered in an extrachromosomal form, i.e., this repeated sequence may work as a transposable element. On the other hand, extrachromosomal DNA can replicate in cells that differentiate from G2. It has been suggested that this is due to the failure of nascent replicons to join when cells reach G2, leaving gaps that serve as recognition sites for the initiation of DNA amplification.61 Hence, the presence of extrachromosomal circular DNA in the terminal cells could support the terminal differentiation hypothesis of the evolution of these cell populations.
Large extracellular vesicles carry most of the tumour DNA circulating in prostate cancer patient plasma
Published in Journal of Extracellular Vesicles, 2018
Tatyana Vagner, Cristiana Spinelli, Valentina R. Minciacchi, Leonora Balaj, Mandana Zandian, Andrew Conley, Andries Zijlstra, Michael R. Freeman, Francesca Demichelis, Subhajyoti De, Edwin M. Posadas, Hisashi Tanaka, Dolores Di Vizio
Using an approach that allows to estimate the size of the intact DNA fragments in EVs, we showed that L-EVs contain unusually high molecular weight DNA. This is the first DNA evaluation directly in intact EVs. Similar size DNA has been reported to derive from DNA damage and likely chromosomal fragmentation that occurs in micronuclei, which can induce chromothripsis [42]. Chromothripsis consists of massive clustered chromosomal rearrangements usually involving one chromosome. This process can induce the formation of double minute chromosomes, which are extrachromosomal circular DNA structures harbouring amplified oncogenes [43–46]. Given the size of L-EVs and their tumour-specific origin, it seems plausible that the extrachromosomal DNA from the cytosol of cancer cells is loaded in L-EVs forming at the plasma membrane. This hypothesis, although speculative, is supported by our data showing that L-EV DNA is chromatinized. However, the molecular mechanisms of DNA loading into EVs are largely unknown and need to be further explored. The nature of L-EV DNA could be interrogated by sequencing the high molecular weight DNA strands, which are uniquely present in L-EVs, to investigate if they are enriched in particular sequences (e.g. amplified oncogenes). In addition, this might also provide some cues to L-EV biogenesis.