Fusion of short telomeres in human cells is characterized by extensive deletion and microhomology, and can result in complex rearrangements.
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All fusion events were characterized by the deletion of at least one of the telomeres extending into the sub-telomeric DNA up to 5.6 kb; close to the limit of the assays.Abstract:
Telomere fusion is an important mutational event that has the potential to lead to large-scale genomic rearrangements of the types frequently observed in cancer. We have developed single-molecule approaches to detect, isolate and characterize the DNA sequence of telomere fusion events in human cells. Using these assays, we have detected complex fusion events that include fusion with interstitial loci adjacent to fragile sites, intra-molecular rearrangements, and fusion events involving the telomeres of both arms of the same chromosome consistent with ring chromosome formation. All fusion events were characterized by the deletion of at least one of the telomeres extending into the sub-telomeric DNA up to 5.6 kb; close to the limit of our assays. The deletion profile indicates that deletion may extend further into the chromosome. Short patches of DNA sequence homology with a G:C bias were observed at the fusion point in 60% of events. The distinct profile that accompanies telomere fusion may be a characteristic of the end-joining processes involved in the fusion event.read more
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Chromothripsis and Kataegis Induced by Telomere Crisis.
TL;DR: It is proposed that chromothripsis in human cancer may arise through TREX1-mediated fragmentation of dicentric chromosomes formed in telomere crisis through the generation of the ssDNA and the resolution of the chromatin bridges.
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Microhomology-Mediated End Joining: A Back-up Survival Mechanism or Dedicated Pathway?
TL;DR: Recent findings pertaining to the mechanism of Microhomology-mediated end joining are reviewed and its role in normal and cancer cells is discussed.
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Telomere length measurement-caveats and a critical assessment of the available technologies and tools.
TL;DR: The goal of this review is to provide a comprehensive summary of the most commonly used methods for telomere length measurement and discuss the advantages and disadvantages of each.
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HEK293 in cell biology and cancer research: phenotype, karyotype, tumorigenicity, and stress-induced genome-phenotype evolution.
A. A. Stepanenko,V. V. Dmitrenko +1 more
TL;DR: In this paper, the authors discussed issues caution against misinterpretations and pitfalls during the different experimental manipulations with 293 cells and discussed the potential to propagate highly neurotropic viruses, inducible synaptogenesis, functionality of the endogenous neuron-specific voltage-gated channels, and response to the diverse agonists implicated in neuronal signaling.
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Bone marrow failure and the telomeropathies
TL;DR: Telomere biology is complexly related to oncogenesis: telomere attrition is protective by enforcing senescence or apoptosis in cells with a long mitotic history, buttelomere loss also can destabilize the genome by chromosome rearrangement and aneuploidy.
References
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TL;DR: Molecular Cloning has served as the foundation of technical expertise in labs worldwide for 30 years as mentioned in this paper and has been so popular, or so influential, that no other manual has been more widely used and influential.
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Telomere shortening associated withchromosome instability isarrested inimmortal cells whichexpress telomerase activity
Christopher M. Counter,Ariel A. Avilion,Catherine E. LeFeuvrel,Carol W. Greider,Calvin B. Harley,A. Steitz +5 more
TL;DR: The results suggest that chromosomes with short (TTAGGG)n tracts are recombinogenic, critically shortened telomeres may be incompatible with cell proliferation and stabilization of telomere length by telomerase may be required for immortalization.
Journal ArticleDOI
Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity.
Christopher M. Counter,A.A. Avilion,C.E. LeFeuvre,N.G. Stewart,Carol W. Greider,Calvin B. Harley,Silvia Bacchetti +6 more
TL;DR: In this article, the authors measured telomere length, telomerase activity and chromosome rearrangements in human cells before and after transformation with SV40 or Ad5 and found that telomeres shortened by approximately 65 bp/generation during the lifespan of the cultures.
Journal ArticleDOI
TRF2 Protects Human Telomeres from End-to-End Fusions
TL;DR: It is shown that the human telomeric protein TRF2 plays a key role in the protective activity of telomeres, and the results raise the possibility that chromosome end fusions and senescence in primary human cells may be caused by loss byTRF2 from shortenedtelomeres.