Title |
PML induces compaction, TRF2 depletion and DNA damage signaling at telomeres and promotes their alternative lengthening
|
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Published in |
Journal of Cell Science, April 2015
|
DOI | 10.1242/jcs.148296 |
Pubmed ID | |
Authors |
Sarah Osterwald, Katharina I. Deeg, Inn Chung, Daniel Parisotto, Stefan Wörz, Karl Rohr, Holger Erfle, Karsten Rippe |
Abstract |
The alternative lengthening of telomeres (ALT) mechanism allows cancer cells to escape senescence and apoptosis in the absence of active telomerase. A characteristic feature of this pathway is the assembly of ALT-associated PML nuclear bodies (APBs) at telomeres. We dissected the role of APBs in a human ALT cell line by RNA interference with an automated 3D fluorescence microscopy platform in conjunction with advanced 3D image analysis. We identified 29 proteins that affected APB formation that were involved in telomere and chromatin organization, protein sumoylation and DNA repair. By integrating and extending these findings we found that APB formation induced clustering of telomere repeats, telomere compaction and concomitant depletion of the shelterin protein TRF2. These APB-dependent changes correlated with the induction of a DNA damage response at colocalizing telomeres via a strong enrichment of the phosphorylated form of the ataxia telangiectasia mutated (ATM) kinase. Accordingly, we propose that APBs promote telomere maintenance by inducing a DNA damage response in ALT-positive tumor cells via changing the telomeric chromatin state to trigger ATM phosphorylation. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
France | 1 | 50% |
Unknown | 1 | 50% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Portugal | 1 | <1% |
Brazil | 1 | <1% |
Unknown | 118 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 33 | 28% |
Student > Master | 20 | 17% |
Researcher | 18 | 15% |
Student > Bachelor | 15 | 13% |
Student > Doctoral Student | 5 | 4% |
Other | 8 | 7% |
Unknown | 21 | 18% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 49 | 41% |
Agricultural and Biological Sciences | 32 | 27% |
Medicine and Dentistry | 6 | 5% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 2% |
Chemistry | 2 | 2% |
Other | 7 | 6% |
Unknown | 22 | 18% |