ArticleNucleic acids research2022
Selective pericentromeric heterochromatin dismantling caused by TP53 activation during senescence.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Crosstalk between lipid metabolism and epigenetics in cellular senescence and age-related diseases.npj aging · 2026Review
- Molecular evolution of animal aging.The EMBO journal · 2026Review
- Integrated epigenetic networks in aging: from histone to RNA modifications.Journal of translational medicine · 2026Review
- Research progress on the spatiotemporal dynamics of therapy-induced senescence in remodeling the tumor microenvironment.Frontiers in immunology · 2026Review
- Satellite DNA fragility accompanies complex genome rearrangements and ecDNA oncogene amplification in canine osteosarcomas.bioRxiv : the preprint server for biology · 2025Article
- Landscape of gene fusions in hormone receptor-positive breast cancer reveals ADK fusions as drivers of progression and potential therapeutic targets.Cell discovery · 2025Article
- hTERT Increases TRF2 to Induce Telomere Compaction and Extend Cell Replicative Lifespan.Aging cell · 2025Article
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- Roles of chromatin and genome instability in cellular senescence and their relevance to ageing and related diseases.Nature reviews. Molecular cell biology · 2024Review
- Article
- Mechanism and role of nuclear laminin B1 in cell senescence and malignant tumors.Cell death discovery · 2024Review
- Non-canonical telomere protection role of FOXO3a of human skeletal muscle cells regulated by the TRF2-redox axis.Communications biology · 2023Article
- Senescence-associated transcriptional derepression in subtelomeres is determined in a chromosome-end-specific manner.Aging cell · 2023Article
- Protein phosphatase 2A activators reverse age-related behavioral changes by targeting neural cell senescence.Aging cell · 2023Article
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Corrections and comments
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Authors and funding
14 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cellular senescence triggers various types of heterochromatin remodeling that contribute to aging. However, the age-related mechanisms that lead to these epigenetic alterations remain elusive. Here, we asked how two key aging hallmarks, telomere shortening and constitutive heterochromatin loss, are mechanistically connected during senescence. We show that, at the onset of senescence, pericentromeric heterochromatin is specifically dismantled consisting of chromatin decondensation, accumulation of DNA breakages, illegitimate recombination and loss of DNA. This process is caused by telomere shortening or genotoxic stress by a sequence of events starting from TP53-dependent downregulation of the telomere protective protein TRF2. The resulting loss of TRF2 at pericentromeres triggers DNA breaks activating ATM, which in turn leads to heterochromatin decondensation by releasing KAP1 and Lamin B1, recombination and satellite DNA excision found in the cytosol associated with cGAS. This TP53-TRF2 axis activates the interferon response and the formation of chromosome rearrangements when the cells escape the senescent growth arrest. Overall, these results reveal the role of TP53 as pericentromeric disassembler and define the basic principles of how a TP53-dependent senescence inducer hierarchically leads to selective pericentromeric dismantling through the downregulation of TRF2.
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