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Persistent telomere cohesion protects aged cells from premature senescence.
- Source :
-
Nature communications [Nat Commun] 2020 Jul 03; Vol. 11 (1), pp. 3321. Date of Electronic Publication: 2020 Jul 03. - Publication Year :
- 2020
-
Abstract
- Human telomeres are bound by the telomere repeat binding proteins TRF1 and TRF2. Telomere shortening in human cells leads to a DNA damage response that signals replicative senescence. While insufficient loading of TRF2 at shortened telomeres contributes to the DNA damage response in senescence, the contribution of TRF1 to senescence induction has not been determined. Here we show that counter to TRF2 deficiency-mediated induction of DNA damage, TRF1 deficiency serves a protective role to limit induction of DNA damage induced by subtelomere recombination. Shortened telomeres recruit insufficient TRF1 and as a consequence inadequate tankyrase 1 to resolve sister telomere cohesion. Our findings suggest that the persistent cohesion protects short telomeres from inappropriate recombination. Ultimately, in the final division, telomeres are no longer able to maintain cohesion and subtelomere copying ensues. Thus, the gradual loss of TRF1 and concomitant persistent cohesion that occurs with telomere shortening ensures a measured approach to replicative senescence.
- Subjects :
- Base Sequence
Cell Line
Cell Line, Tumor
Cellular Senescence genetics
DNA Damage
HEK293 Cells
Heterochromatin genetics
Heterochromatin metabolism
Humans
In Situ Hybridization, Fluorescence
Mutation
RNA Interference
Tankyrases metabolism
Telomere metabolism
Telomeric Repeat Binding Protein 1 deficiency
Telomeric Repeat Binding Protein 1 metabolism
Telomeric Repeat Binding Protein 2 deficiency
Telomeric Repeat Binding Protein 2 metabolism
Telomere genetics
Telomere Shortening genetics
Telomeric Repeat Binding Protein 1 genetics
Telomeric Repeat Binding Protein 2 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 32620872
- Full Text :
- https://doi.org/10.1038/s41467-020-17133-4