Telomere elongation is coupled with genome replication, raising the question of the repair of short telomeres in post-mitotic cells. We investigated the fate of a telomere-repeat capped end that mimics a single short telomere in quiescent fission yeast cells. We show that telomerase is able to elongate this single short telomere during quiescence despite the binding of Ku to the proto-telomere. While Taz1 and Rap1 repress telomerase in vegetative cells, both shelterin proteins are required for efficient telomere extension in quiescent cells, underscoring a distinct mode of telomerase control. We further show that Rad3ATR and Tel1ATM are redundantly required for telomere elongation in quiescence through the phosphorylation of Ccq1 and that Rif1 and its associated-PP1 phosphatases negatively regulate telomerase activity by opposing Ccq1 phosphorylation. The distinct mode of telomerase regulation in quiescent fission yeast cells may be relevant to that in human stem and progenitor cells.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9723628 | PMC |
| http://dx.doi.org/10.1093/nar/gkac986 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Unlabelled: Quantitative understanding of mitochondrial heterogeneity is necessary for elucidating the precise role of these multifaceted organelles in tumor cell development. We demonstrate an early mechanistic role of mitochondria in initiating neoplasticity by performing quantitative analyses of structure-function of single mitochondrial components coupled with single cell transcriptomics. We demonstrate that the large Hyperfused-Mitochondrial-Networks (HMNs) of keratinocytes promptly get converted to the heterogenous Small-Mitochondrial-Networks (SMNs) as the stem cell enriching dose of the model carcinogen, TCDD, depolarizes mitochondria.
View Article and Find Full Text PDFThe Greatwall-Endosulfine-PP2A/B55 pathway regulates entry into quiescence by enhancing translation of Elongator-tunable transcripts.
Nat Commun
December 2024
Instituto de Biología Funcional y Genómica, CSIC, University of Salamanca, 37007, Salamanca, Spain.
Quiescent cells require a continuous supply of proteins to maintain protein homeostasis. In fission yeast, entry into quiescence is triggered by nitrogen stress, leading to the inactivation of TORC1 and the activation of TORC2. In this study, we demonstrate that the Greatwall-Endosulfine-PPA/B55 pathway connects the downregulation of TORC1 with the upregulation of TORC2, resulting in the activation of Elongator-dependent tRNA modifications crucial for sustaining the translation programme during entry into quiescence.
View Article and Find Full Text PDFMapping Active RNA Polymerases in Proliferating and Quiescent Fission Yeast Cells Using Precision Run-On Sequencing.
Methods Mol Biol
November 2024
Institute of Biochemistry and Cellular Genetics, CNRS UMR 5095 and University of Bordeaux, Bordeaux, France.
The development of next-generation sequencing (NGS) approaches to investigate the functioning of RNA polymerases has led to groundbreaking advances in the field of transcriptional regulation. One powerful method, Precision nuclear Run-On sequencing (PRO-seq), maps the locations of RNA polymerase active sites genome-wide at high resolution. PRO-seq provides a snapshot of strand-specific transcriptional activity and does not rely on immunoprecipitation of the polymerase of interest.
View Article and Find Full Text PDFEpigenome Mapping in Quiescent Cells Reveals a Key Role for H3K4me3 in Regulation of RNA Polymerase II Activity.
Epigenomes
October 2024
Department of Medicine Huddinge, Division of Biosciences and Nutrition, Karolinska Institute, NEO Building, SE-141-83 Huddinge, Sweden.
(1) Background: Quiescent cells are those that have stopped dividing and show strongly reduced levels of gene expression during dormancy. In response to appropriate signals, the cells can wake up and start growing again. Many histone modifications are regulated in quiescence, but their exact functions remain to be determined.
View Article and Find Full Text PDFTumor microenvironment induced switch to mitochondrial metabolism promotes suppressive functions in immune cells.
Int Rev Cell Mol Biol
October 2024
Department of Radiation Oncology, Montefiorke Medical Center, Bronx, NY, United States; Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, United States.
Understanding the intricacies of the metabolic phenotype in immune cells and its plasticity within the tumor microenvironment is pivotal in understanding the pathology and prognosis of cancer. Unfavorable conditions and cellular stress in the tumor microenvironment (TME) exert a profound impact on cellular functions in immune cells, thereby influencing both tumor progression and immune responses. Elevated AMP:ATP ratio, a consequence of limited glucose levels, activate AMP-activated protein kinase (AMPK) while concurrently repressing the activity of mechanistic target of rapamycin (mTOR) and hypoxia-inducible factor 1-alpha (HIF-1α).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!