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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Rap1 relocalization contributes to the chromatin-mediated gene expression profile and pace of cell senescence
Genes and Development, Volume 27, No. 12, Year 2013
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Description
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 upregulated 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. © 2013 by Cold Spring Harbor Laboratory Press.
Authors & Co-Authors
Platt, Jesse M.
United States, Philadelphia
University of Pennsylvania
Ryvkin, Paul
United States, Philadelphia
University of Pennsylvania
Wanat, Jennifer J.
United States, Philadelphia
University of Pennsylvania
Donahue, Greg
United States, Philadelphia
University of Pennsylvania
Ricketts, M. Dan
United States, Philadelphia
The Wistar Institute
Barrett, Steven P.
United States, Swarthmore
Swarthmore College
Waters, Hannah J.
United States, Philadelphia
University of Pennsylvania
Song, Shufei
United States, Philadelphia
University of Pennsylvania
Chavez, Alejandro
United States, Philadelphia
University of Pennsylvania
United States, Boston
Massachusetts General Hospital
Abdallah, Khaled Omar
United States, Philadelphia
University of Pennsylvania
Egypt, Cairo
Ain Shams University
Master, Stephen R.
United States, Philadelphia
University of Pennsylvania
Wang, Li San
United States, Philadelphia
University of Pennsylvania
Johnson, F. Brad
United States, Philadelphia
University of Pennsylvania
Statistics
Citations: 76
Authors: 13
Affiliations: 5
Identifiers
Doi:
10.1101/gad.218776.113
ISSN:
08909369
e-ISSN:
15495477
Research Areas
Cancer
Genetics And Genomics