ArticleGenes & development2013
Rap1 relocalization contributes to the chromatin-mediated gene expression profile and pace of cell senescence.
Article in Genes & development, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
57 citing papers in PubMed, 88 citations in OpenAlex.
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- Unraveling Histone Loss in Aging and Senescence.Cells · 2024Review
- ΔNp63α-mediated epigenetic regulation in keratinocyte senescence.Epigenetics · 2023Article
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- Telomere Checkpoint in Development and Aging.International journal of molecular sciences · 2023Review
- Senescence-associated transcriptional derepression in subtelomeres is determined in a chromosome-end-specific manner.Aging cell · 2023Article
- Telomeres are shorter in wild Saccharomyces cerevisiae isolates than in domesticated ones.Genetics · 2023Article
- Possible molecular mechanisms underlying the development of atherosclerosis in cancer survivors.Frontiers in cardiovascular medicine · 2023Review
- Telomeres expand sphere of influence: emerging molecular impact of telomeres in non-telomeric functions.Trends in genetics : TIG · 2023Review
- Aberrant expression and localization of the RAP1 shelterin protein contribute to age-related phenotypes.PLoS genetics · 2022Article
- Tieing together loose ends: telomere instability in cancer and aging.Molecular oncology · 2022Review
- Stem cells at odds with telomere maintenance and protection.Trends in cell biology · 2022Review
- Rap1 regulates TIP60 function during fate transition between two-cell-like and pluripotent states.Genes & development · 2022Article
- Distinct structural groups of histone H3 and H4 residues have divergent effects on chronological lifespan in Saccharomyces cerevisiae.PloS one · 2022Article
- Review
- Cellular aging beyond cellular senescence: Markers of senescence prior to cell cycle arrest in vitro and in vivo.Aging cell · 2021Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Cellular senescence is accompanied by dramatic changes in chromatin structure and gene expression. Using Saccharomyces cerevisiae mutants lacking telomerase (tlc1Δ) to model senescence, we found that with critical telomere shortening, the telomere-binding protein Rap1 (repressor activator protein 1) relocalizes to the upstream promoter regions of hundreds of new target genes. The set of new Rap1 targets at senescence (NRTS) is preferentially activated at senescence, and experimental manipulations of Rap1 levels indicate that it contributes directly to NRTS activation. A notable subset of NRTS includes the core histone-encoding genes; we found that Rap1 contributes to their repression and that histone protein levels decline at senescence. Rap1 and histones also display a target site-specific antagonism that leads to diminished nucleosome occupancy at the promoters of up-regulated NRTS. This antagonism apparently impacts the rate of senescence because underexpression of Rap1 or overexpression of the core histones delays senescence. Rap1 relocalization is not a simple consequence of lost telomere-binding sites, but rather depends on the Mec1 checkpoint kinase. Rap1 relocalization is thus a novel mechanism connecting DNA damage responses (DDRs) at telomeres to global changes in chromatin and gene expression while driving the pace of senescence.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.