Synthetic construct
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA326221 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR3696100.fastq.gz | Fastqsanger.gz | |||
| SRR3696101.fastq.gz | Fastqsanger.gz | |||
| SRR3696102.fastq.gz | Fastqsanger.gz | |||
| SRR3696103.fastq.gz | Fastqsanger.gz | |||
| SRR3696104.fastq.gz | Fastqsanger.gz |
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Project description:Telomere is a highly refined system for maintaining the stability of linear chromosomes. Most telomeres rely on simple repetitive sequences and telomerase enzymes, but in some species or telomerase-defective situations, alternative telomere lengthening (ALT) mechanism is utilized to protect chromosomal ends. Telomere loss can induce telomere recombination by which specific sequences can be recruited into telomeres. However, canonical telomeric repeat-based telomeres have been found in mammals. Here, we show that mammalian telomeres can also be completely reconstituted using a non-telomeric unique sequence. We found that a specific subtelomeric element, named as mouse template for ALT (mTALT), is utilized for repairing telomeric DNA damage and composing new telomeric sequences in mouse embryonic stem cells. We found a high-level of non-coding mTALT transcript despite the heterochromatic nature of mTALT-based telomere. After ALT activation, the increased HMGN1, a non-histone chromosomal protein, contributed to maintaining telomere stability by regulating telomeric transcriptions. Our findings reveal novel molecular features of potential telomeric sequences which can reconstitute telomeres during cancer formation and evolution.
2020-07-17 | MSV000085772 | MassIVE
Project description:Cytosine methylation regulates the length and stability of telomeres, which can affect a wide variety of biological features including cell differentiation, development or illness. Whereas it is well established that subtelomeric regions are methylated, the presence of methylated cytosines at telomeres has remained controversial. Here, we have analyzed multiple bisulfite sequencing studies to address the methylation status of Arabidopsis thaliana telomeres. We found that the levels of telomeric DNA methylation estimated varied among studies. Interestingly, we estimated higher levels of telomeric DNA methylation in studies that produced C-rich telomeric strands with lower efficiency. However, these high methylation estimates arose due to experimental limitations of the bisulfite technique. We found a similar phenomenom for mitochondrial DNA: the levels of mitochondrial DNA methylation detected were higher in experiments with lower mitochondrial read production efficiencies. Based on experiments with high telomeric C-rich strand production efficiencies, we concluded that Arabidopsis telomeres are not methylated, which was confirmed by methylation dependent restriction enzymes analyses. Thus, our studies indicate that telomeres are refractory to de novo DNA methylation by the RNA directed DNA methylation machinery. This result, together with previously reported data, reveals that subtelomeric DNA methylation controls the homeostasis of telomere length.
2016-06-21 | GSE83510 | GEO
Project description:Context Influences on TALE-DNA Binding Revealed by Quantitative Profiling
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Project description:Global analysis of Drosophila Cys2-His2 zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants.
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Project description:Most sarcomas have complex karyotype and are characterized by multiple chromosomal rearrangements. Moreover, sarcomas very frequently maintain their telomeres by recombination in the process called Alternative Lengthening of Telomeres (ALT) which enables their continuous growth and immortalization. Previously our group showed that orphan receptors bind specifically to the ALT telomeres and that their presence is important for the ALT mechanism. In these studies we focus on the function of orphan receptors at the telomeres and their contribution to telomeric recombination. We demonstrate that orphan receptors induce proximity of their binding sites in telomeric and genomic context and reveal novel aspects of ALT which are telomere-genome rearrangements which can underlie complexity of sarcomas. Our data perturb the dogma of telomere function in protecting the genome integrity. Here we show that in some cases telomeres may in fact drive genomic instability and chromosomal rearrangements by recombination with genomic sites. Characterization of TRF2 and orphan receptor NR2F/C2 binding sites in ALT (-) and ALT (+) cells.
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Project description:We performed single-molecule telomere length and telomere fusion analysis in patients at different stages of chronic lymphocytic leukaemia (CLL). Our work identified the shortest telomeres ever recorded in primary human tissue reinforcing the concept that there is significant cell division in CLL. Furthermore, we provide direct evidence that critical telomere shortening, dysfunction and fusion contribute to disease progression. The frequency of short telomeres and fusion events increased with advanced disease, but importantly these were also found in a subset of early-stage patient samples indicating that these events can precede disease progression. Sequence analysis of fusion events isolated from individuals with the shortest telomeres revealed limited numbers of repeats at the breakpoint, sub-telomeric deletion and microhomology. Array-CGH analysis of individuals displaying evidence of telomere dysfunction revealed large-scale genomic rearrangements that were concentrated in the telomeric regions; this was not observed in samples with longer telomeres. Array CGH was undertaken on six individuals (five CLL stage C and one stage A) that displayed evidence of telomere dysfunction, and four (three CLL stage A and one stage B) that displayed longer and apparently stable telomeres.
2010-05-28 | E-GEOD-22016 | biostudies-arrayexpress
Project description:Protein phosphatase magnesium-dependent 1 delta (PPM1D) terminates the cell cycle checkpoint by dephosphorylating the tumour suppressor protein p53. By targeting additional substrates at chromatin, PPM1D contributes to the control of DNA damage response and DNA repair. Using proximity biotinylation followed by proteomic analysis, we identified a novel interaction between PPM1D and the shelterin complex that protects telomeric DNA. In addition, confocal microscopy revealed that endogenous PPM1D colocalized with TRF2 at telomeres. Further, we found that ATR phosphorylated TRF2 at S410 after induction of DNA double strand breaks at telomeres and this modification increased after inhibition or loss of PPM1D. TRF2 phosphorylation stimulated its interaction with TIN2 both in vitro and at telomeres. Conversely, induced expression of PPM1D impaired localisation of TIN2 and TPP1 at telomeres. Finally, recruitment of the DNA repair factor 53BP1 to the telomeric breaks was strongly reduced after inhibition of PPM1D and was rescued by the expression of TRF2-S410A mutant. Our results suggest that TRF2 phosphorylation promotes the association of TIN2 within the shelterin complex and regulates DNA repair at telomeres.
2023-03-11 | PXD035273 | Pride
Project description:Oxidative stress is a primary cause of cellular senescence and contributes to the pathogenesis of numerous human diseases. Oxidative damage to telomeric DNA is proposed to trigger premature senescence by accelerating telomere shortening. Here we tested this model directly using a precision tool to produce the common base lesion 8-oxoguanine (8oxoG) exclusively at telomeres in human fibroblast and epithelial cells. A single induction of telomeric 8oxoG is sufficient to trigger multiple hallmarks of p53-dependent senescence. Telomeric 8oxoG activates ATM and ATR signaling, and enriches for markers of telomere dysfunction in replicating, but not quiescent cells. Acute 8oxoG production fails to shorten telomeres, but rather generates fragile sites and delayed mitotic DNA synthesis at telomeres, indicative of impaired replication. Based on our results we propose that oxidative stress promotes rapid senescence by producing oxidative base lesions which drive replication-dependent telomere fragility and dysfunction in the absence of shortening and shelterin loss.
2022-05-26 | GSE175686 | GEO
Project description:We performed single-molecule telomere length and telomere fusion analysis in patients at different stages of chronic lymphocytic leukaemia (CLL). Our work identified the shortest telomeres ever recorded in primary human tissue reinforcing the concept that there is significant cell division in CLL. Furthermore, we provide direct evidence that critical telomere shortening, dysfunction and fusion contribute to disease progression. The frequency of short telomeres and fusion events increased with advanced disease, but importantly these were also found in a subset of early-stage patient samples indicating that these events can precede disease progression. Sequence analysis of fusion events isolated from individuals with the shortest telomeres revealed limited numbers of repeats at the breakpoint, sub-telomeric deletion and microhomology. Array-CGH analysis of individuals displaying evidence of telomere dysfunction revealed large-scale genomic rearrangements that were concentrated in the telomeric regions; this was not observed in samples with longer telomeres.
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