Advertisement

Topics

TERRA and the histone methyltransferase Dot1 cooperate to regulate senescence in budding yeast.

08:00 EDT 12th April 2018 | BioPortfolio

Summary of "TERRA and the histone methyltransferase Dot1 cooperate to regulate senescence in budding yeast."

The events underlying senescence induced by critical telomere shortening are not fully understood. Here we provide evidence that TERRA, a non-coding RNA transcribed from subtelomeres, contributes to senescence in yeast lacking telomerase (tlc1Δ). Levels of TERRA expressed from multiple telomere ends appear elevated at senescence, and expression of an artificial RNA complementary to TERRA (anti-TERRA) binds TERRA in vivo and delays senescence. Anti-TERRA acts independently from several other mechanisms known to delay senescence, including those elicited by deletions of EXO1, TEL1, SAS2, and genes encoding RNase H enzymes. Further, it acts independently of the senescence delay provided by RAD52-dependent recombination. However, anti-TERRA delays senescence in a fashion epistatic to inactivation of the conserved histone methyltransferase Dot1. Dot1 associates with TERRA, and anti-TERRA disrupts this interaction in vitro and in vivo. Surprisingly, the anti-TERRA delay is independent of the C-terminal methyltransferase domain of Dot1 and instead requires only its N-terminus, which was previously found to facilitate release of telomeres from the nuclear periphery. Together, these data suggest that TERRA and Dot1 cooperate to drive senescence.

Affiliation

Journal Details

This article was published in the following journal.

Name: PloS one
ISSN: 1932-6203
Pages: e0195698

Links

DeepDyve research library

PubMed Articles [3825 Associated PubMed Articles listed on BioPortfolio]

Increased TERRA levels and RNase H sensitivity are conserved hallmarks of post-senescent survivors in budding yeast.

Cancer cells activate telomere maintenance mechanisms (TMMs) to bypass replicative senescence and achieve immortality by either upregulating telomerase or promoting homology-directed repair (HDR) at c...

Inflammatory factor receptor Toll-like receptor 4 controls telomeres through heterochromatin protein 1 isoforms in liver cancer stem cell.

Toll-like receptor 4 (TLR4) which acts as a receptor for lipopolysaccharide (LPS) has been reported to be involved in carcinogenesis. However, the regulatory mechanism of it has not been elucidated. H...

Regulation of Cellular Senescence by Polycomb Chromatin Modifiers through Distinct DNA Damage- and Histone Methylation-Dependent Pathways.

Polycomb group (PcG) factors maintain facultative heterochromatin and mediate many important developmental and differentiation processes. EZH2, a PcG histone H3 lysine-27 methyltransferase, is repress...

Unveiling epidithiodiketopiperazine as a non-histone arginine methyltransferase inhibitor by chemical protein methylome analyses.

We present a chemical methylome analysis platform to evaluate the inhibitory activity of small molecules towards poorly characterized protein methyltransferases (PMTs), facsilitating to identify syn-H...

Identification of a peptide inhibitor for the histone methyltransferase WHSC1.

WHSC1 is a histone methyltransferase that is responsible for mono- and dimethylation of lysine 36 on histone H3 and has been implicated as a driver in a variety of hematological and solid tumors. Curr...

Clinical Trials [422 Associated Clinical Trials listed on BioPortfolio]

Anti-thymocyte Globulin-induced Immune Senescence

The aim of the study is to investigate the impact of Anti-Thymocyte Globulin (ATG) on immune senescence. Markers of immune senescence expression is assessed in a prospective cohort of rena...

Epigenetic Regulation of Immunity in Alpha-1 Anti-trypsin Deficiency

The investigators hypothesize that environmentally influenced histone modifications regulate AM mediated inflammation, contributing to a variable clinical course of AATD, and may also infl...

Impact of Endothelial and Leukocyte Senescence in Circulatory Shock States

Circulatory shocks (CS) are life-threatening, acute organ dysfunction. Advances in critical care medicine have decreased early hospital mortality, increasing the number of surviving patien...

Intratumoral Budding (ITB) in Preoperative Biopsies of Colon and Rectal Cancer

All the preoperative biopsies of patients suffering colorectal cancer (CRC) will be immunohistochemically stained with a pancytokeratin marker to detect Tumor buds. then, the intratumoral ...

Cognitive Changes Associated With Breast Cancer Treatment

Patients with cancer often complain that their "mind does not seem to be clear." This can be due to stress, depression, anxiety, or physical problems caused by cancer or the treatments use...

Medical and Biotech [MESH] Definitions

A histone-lysine N-methyltransferase and catalytic subunit of Polycomb Repressive Complex 2. It methylates LYSINE 9 (H3K9me) and LYSINE 27 (H3K27me) of HISTONE H3, leading to transcriptional repression of the affected target gene. EZH2 also methylates non-histone proteins such as GATA4 TRANSCRIPTION FACTOR and the nuclear receptor RORA. It regulates CIRCADIAN CLOCKS via histone methylation at the PROMOTER REGIONS of the circadian genes and its repressive activity is also important for the identity and differentiation of EMBRYONIC STEM CELLS.

A class II histone deacetylase that removes acetyl groups from N-terminal LYSINES of HISTONE H2A; HISTONE H2B; HISTONE H3; and HISTONE H4. It plays a critical role in EPIGENETIC REPRESSION and regulation of GENETIC TRANSCRIPTION, as well as CELL MOTILITY through deacetylation of TUBULIN. It also targets misfolded proteins for clearance by AUTOPHAGY when MOLECULAR CHAPERONE-mediated folding is overwhelmed.

Process by which cells irreversibly stop dividing and enter a state of permanent growth arrest without undergoing CELL DEATH. Senescence can be induced by DNA DAMAGE or other cellular stresses, such as OXIDATIVE STRESS.

An enzyme that catalyzes the methylation of the epsilon-amino group of lysine residues in proteins to yield epsilon mono-, di-, and trimethyllysine. EC 2.1.1.43.

Subpopulation of CD4+ lymphocytes that cooperate with other lymphocytes (either T or B) to initiate a variety of immune functions. For example, helper-inducer T-cells cooperate with B-cells to produce antibodies to thymus-dependent antigens and with other subpopulations of T-cells to initiate a variety of cell-mediated immune functions.

Advertisement
Quick Search
Advertisement
Advertisement

 


DeepDyve research library

Relevant Topic

Complementary and Alternative Medicine
Alternative medicine are whole medical systems that did not fit with conventional medicine as they have completely different philosophies and ideas on the causes of disease, methods of diagnosis and approaches to treatment. Although often overlapping, co...


Searches Linking to this Article