scholarly journals Intrachromosomal Changes and Genomic Instability in Site-Specific Microbeam-Irradiated and Bystander Human-Hamster Hybrid Cells

2012 ◽  
Vol 177 (1) ◽  
pp. 25-34 ◽  
Author(s):  
Burong Hu ◽  
Peter Grabham ◽  
Jing Nie ◽  
Adayabalam S. Balajee ◽  
Hongning Zhou ◽  
...  
Keyword(s):  
Genomic Instability ◽  
Hybrid Cells ◽  
Site Specific

scholarly journals Supercoiling and looping promote DNA base accessibility and coordination among distant sites

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jonathan M. Fogg ◽  
Allison K. Judge ◽  
Erik Stricker ◽  
Hilda L. Chan ◽  
Lynn Zechiedrich
Keyword(s):  
Mechanical Stress ◽  
Genomic Instability ◽  
Base Pair ◽  
Base Pairing ◽  
Complex Interplay ◽  
Site Specific ◽  
Torsional Strain ◽  
Dna Base ◽  
Dna Backbone ◽  
Negative Supercoiling

AbstractDNA in cells is supercoiled and constrained into loops and this supercoiling and looping influence every aspect of DNA activity. We show here that negative supercoiling transmits mechanical stress along the DNA backbone to disrupt base pairing at specific distant sites. Cooperativity among distant sites localizes certain sequences to superhelical apices. Base pair disruption allows sharp bending at superhelical apices, which facilitates DNA writhing to relieve torsional strain. The coupling of these processes may help prevent extensive denaturation associated with genomic instability. Our results provide a model for how DNA can form short loops, which are required for many essential processes, and how cells may use DNA loops to position nicks to facilitate repair. Furthermore, our results reveal a complex interplay between site-specific disruptions to base pairing and the 3-D conformation of DNA, which influences how genomes are stored, replicated, transcribed, repaired, and many other aspects of DNA activity.

Genomic instability in mammalian cell hybrids. IV. Is mutation frequency elevated in hybrid cells?

1990 ◽  
Vol 69 (2) ◽  
pp. 79-86
Author(s):  
Robert Center ◽  
Jaclyn M. Watson ◽  
Lynne Mckay ◽  
Rosalia Bruzzese ◽  
Jennifer A. Marshall Graves
Keyword(s):  
Genomic Instability ◽  
Mammalian Cell ◽  
Mutation Frequency ◽  
Hybrid Cells ◽  
Cell Hybrids

scholarly journals Cell Fusion-Mediated Tissue Regeneration as an Inducer of Polyploidy and Aneuploidy

2020 ◽  
Vol 21 (5) ◽  
pp. 1811 ◽  
Author(s):  
Jessica Dörnen ◽  
Mareike Sieler ◽  
Julian Weiler ◽  
Silvia Keil ◽  
Thomas Dittmar
Keyword(s):  
Genomic Instability ◽  
Cell Fusion ◽  
Tissue Regeneration ◽  
Hybrid Cells ◽  
Daughter Cells ◽  
Physiological Processes ◽  
Multipolar Spindles ◽  
First Results ◽  
Random Segregation ◽  
A Cell

The biological phenomenon of cell fusion plays a crucial role in several physiological processes, including wound healing and tissue regeneration. Here, it is assumed that bone marrow-derived stem cells (BMSCs) could adopt the specific properties of a different organ by cell fusion, thereby restoring organ function. Cell fusion first results in the production of bi- or multinucleated hybrid cells, which either remain as heterokaryons or undergo ploidy reduction/heterokaryon-to-synkaryon transition (HST), thereby giving rise to mononucleated daughter cells. This process is characterized by a merging of the chromosomes from the previously discrete nuclei and their subsequent random segregation into daughter cells. Due to extra centrosomes concomitant with multipolar spindles, the ploidy reduction/HST could also be associated with chromosome missegregation and, hence, induction of aneuploidy, genomic instability, and even putative chromothripsis. However, while the majority of such hybrids die or become senescent, aneuploidy and genomic instability appear to be tolerated in hepatocytes, possibly for stress-related adaption processes. Likewise, cell fusion-induced aneuploidy and genomic instability could also lead to a malignant conversion of hybrid cells. This can occur during tissue regeneration mediated by BMSC fusion in chronically inflamed tissue, which is a cell fusion-friendly environment, but is also enriched for mutagenic reactive oxygen and nitrogen species.

scholarly journals Cell–cell fusion of mesenchymal cells with distinct differentiations triggers genomic and transcriptomic remodelling toward tumour aggressiveness

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Lucile Delespaul ◽  
Caroline Gélabert ◽  
Tom Lesluyes ◽  
Sophie Le Guellec ◽  
Gaëlle Pérot ◽  
...  
Keyword(s):  
Genomic Instability ◽  
Cell Fusion ◽  
Mesenchymal Cells ◽  
Tumour Cells ◽  
Physiological Process ◽  
Hybrid Cells ◽  
Transcriptomic Profile ◽  
Transformed Fibroblasts ◽  
Histological Characteristics ◽  
Cell Cell

AbstractCell–cell fusion is a physiological process that is hijacked during oncogenesis and promotes tumour evolution. The main known impact of cell fusion is to promote the formation of metastatic hybrid cells following fusion between mobile leucocytes and proliferating tumour cells. We show here that cell fusion between immortalized myoblasts and transformed fibroblasts, through genomic instability and expression of a specific transcriptomic profile, leads to emergence of hybrid cells acquiring dissemination properties. This is associated with acquisition of clonogenic ability by fused cells. In addition, by inheriting parental properties, hybrid tumours were found to mimic the histological characteristics of a specific histotype of sarcomas: undifferentiated pleomorphic sarcomas with incomplete muscular differentiation. This finding suggests that cell fusion, as macroevolution event, favours specific sarcoma development according to the differentiation lineage of parent cells.

scholarly journals CpG site-specific RASSF1a hypermethylation is associated with occupational PAH exposure and genomic instability

2015 ◽  
Vol 4 (4) ◽  
pp. 848-857 ◽  
Author(s):  
Zhini He ◽  
Huawei Duan ◽  
Biao Zhang ◽  
Miao Li ◽  
Liping Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Genomic Instability ◽  
Cancer Development ◽  
Site Specific ◽  
Cpg Site ◽  
Pah Exposure

Previous studies have shown an etiologic link between exposure to PAHs and lung cancer development.

Large-cluster and combined fluorescent and gold immunoprobes

1996 ◽  
Vol 54 ◽  
pp. 892-893
Author(s):  
Richard D. Powell ◽  
James F. Hainfeld ◽  
Carol M. R. Halsey ◽  
David L. Spector ◽  
Shelley Kaurin ◽  
...  
Keyword(s):  
Metal Cluster ◽  
Sulfonyl Chloride ◽  
Gel Filtration ◽  
Cross Linking ◽  
Site Specific ◽  
Fab Fragments ◽  
Cluster Label ◽  
Covalently Linked ◽  
Texas Red ◽  
Fold Excess

Two new types of covalently linked, site-specific immunoprobes have been prepared using metal cluster labels, and used to stain components of cells. Combined fluorescein and 1.4 nm “Nanogold” labels were prepared by using the fluorescein-conjugated tris (aryl) phosphine ligand and the amino-substituted ligand in the synthesis of the Nanogold cluster. This cluster label was activated by reaction with a 60-fold excess of (sulfo-Succinimidyl-4-N-maleiniido-cyclohexane-l-carboxylate (sulfo-SMCC) at pH 7.5, separated from excess cross-linking reagent by gel filtration, and mixed in ten-fold excess with Goat Fab’ fragments against mouse IgG (obtained by reduction of F(ab’)2 fragments with 50 mM mercaptoethylamine hydrochloride). Labeled Fab’ fragments were isolated by gel filtration HPLC (Superose-12, Pharmacia). A combined Nanogold and Texas Red label was also prepared, using a Nanogold cluster derivatized with both and its protected analog: the cluster was reacted with an eight-fold excess of Texas Red sulfonyl chloride at pH 9.0, separated from excess Texas Red by gel filtration, then deprotected with HC1 in methanol to yield the amino-substituted label.

The challenge of detecting modifications on proteins

2020 ◽  
Vol 64 (1) ◽  
pp. 135-153 ◽  
Author(s):  
Lauren Elizabeth Smith ◽  
Adelina Rogowska-Wrzesinska
Keyword(s):  
Mass Spectrometry ◽  
Protein Function ◽  
Chemical Properties ◽  
Lysine Acetylation ◽  
Mass Determination ◽  
Post Translational Modifications ◽  
Site Specific ◽  
The Common

Abstract Post-translational modifications (PTMs) are integral to the regulation of protein function, characterising their role in this process is vital to understanding how cells work in both healthy and diseased states. Mass spectrometry (MS) facilitates the mass determination and sequencing of peptides, and thereby also the detection of site-specific PTMs. However, numerous challenges in this field continue to persist. The diverse chemical properties, low abundance, labile nature and instability of many PTMs, in combination with the more practical issues of compatibility with MS and bioinformatics challenges, contribute to the arduous nature of their analysis. In this review, we present an overview of the established MS-based approaches for analysing PTMs and the common complications associated with their investigation, including examples of specific challenges focusing on phosphorylation, lysine acetylation and redox modifications.

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