Telomere homeostasis is regulated by telomerase and a collection of associated proteins. Telomerase is, in turn, post-translational modifications the rate-limiting catalytic subunit hTERT. Here we show that disruption Hsp90 geldanamycin promotes efficient ubiquitination proteasome-mediated degradation Furthermore, have used yeast two-hybrid method to identify novel RING finger gene ( MKRN1 ) encoding an E3 ligase mediates Overexpression telomerase-positive cells hTERT decreases activity...

Alternating purine-pyrimidine sequences (RY repeats) demonstrate considerable homology to the consensus sequence for vertebrate topoisomerase 11 (Spitzner and Muller (1988) Nucleic Acids Res.16: 1533-1556).This is shown below positions that can match are underscored.RYRYRYRYRYRYRYRYRY = alternating purine-RNYNNCNNGYNGKTNYNY pyrimidine 18 bp (R purine, Y pyrimidine, K G or T.) Topoisomerase cleavage reactions were performed (in absence of inhibitors) on a plasmid containing 54 base RY repeat...

Sustained cell proliferation requires telomerase to maintain functional telomeres that are essential for chromosome integrity and protection. Although nuclear import of hTERT is required activity elongate in vivo, the molecular mechanism regulating localization unclear. Here we identify a bipartite signal (NLS) (amino acid residues 222–240) responsible hTERT. Immunofluorescence imaging revealed mutations any NLS sequences result decreased fluorescence intensity compared wild-type We also...

Topoisomerase II is the cytotoxic target for a number of clinically relevant antitumor drugs. Berberrubine, protoberberine alkaloid which exhibits activity in animal models, has been identified as specific poison topoisomerase vitro. II-mediated DNA cleavage assays showed that berberrubine poisons enzyme by stabilizing II-DNA cleavable complexes. Subsequent proteinase K treatments revealed berberrubine-induced was generated solely II. religation with elevated temperature substantial...

We have identified a rice gene encoding DNA-binding protein that specifically recognizes the telomeric repeat sequence TTTAGGG found in plants. This gene, which we refer to asRTBP1 (rice telomere-binding 1), encodes polypeptide with predicted molecular mass of 70 kDa. RTBP1 is ubiquitously expressed various organs and binds DNA two or more duplex repeats. The includes single domain at C terminus extensive homology Myb-like binding motif. very closely related other proteins, including TRF1,...

Summary Telomere homeostasis, a process that is essential for the maintenance of chromosome integrity, regulated by telomerase and collection associated proteins. By mass spectrometry we have identified new telomeric protein encoded AtWHY1 ( Arabidopsis thaliana Whirly 1) gene in Arabidopsis. specifically binds single‐stranded plant DNA sequences, but not double‐stranded DNA. To gain insights into function telomere biogenesis, two lines harboring T‐DNA insertions . These exhibit neither...

Human diploid fibroblasts have the capacity to complete a finite number of cell divisions before entering state replicative senescence characterized by growth arrest, changes in morphology, and altered gene expression. Herein, we report that interaction with extracellular matrix (ECM) from young cells is sufficient restore aged, senescent an apparently youthful state. The identity restored as having been derived has confirmed variety methods, including time lapse live imaging DNA finger...

The maintenance of eukaryotic telomeres requires telomerase, which is minimally composed a telomerase reverse transcriptase (TERT) and an associated RNA component. Telomerase activity tightly regulated by expression human (h) TERT at both the transcriptional post-translational levels. Hsp90 p23 molecular chaperones have been shown to associate with hTERT for assembly active telomerase. Here, we show that CHIP (C terminus Hsc70-interacting protein) physically associates in cytoplasm regulates...

The telomeric protein TRF1 negatively regulates telomere length by inhibiting telomerase access at the termini, suggesting that level of telomeres is tightly regulated. Regulation abundance essential for proper function and occurs primarily through post-translational modifications TRF1. Here we describe RLIM, a RING H2 zinc finger with intrinsic ubiquitin ligase activity, as TRF1-interacting protein. RLIM increases turnover targeting it degradation proteasome in ubiquitin-dependent manner,...

Summary Human chromosome ends associate with shelterin, a six‐protein complex that protects telomeric DNA from being recognized as sites of damage. The shelterin subunit TRF2 has been implicated in the protection by facilitating their organization into protective capping structure and associating several accessory proteins involved various transactions. Here we describe characterization DDX39 DEAD‐box RNA helicase novel TRF2‐interacting protein. directly interacts repeat binding factor...

Cellular senescence can be induced by high levels of reactive oxygen species (ROS) produced mitochondria. However, the mechanism which elevated mitochondrial ROS are during replicative is not yet fully understood. Here, we report that loss RNA-binding protein, human antigen R (HuR), leads to an increase in through enhanced localization telomeric protein TIN2. HuR binds 3' untranslated region TIN2 mRNA. This association decreases both destabilizing mRNA and reducing its translation....

Telomerase activity is expressed in most types of cancer cells but not normal somatic cells, suggesting that telomerase may be an important target for chemotherapy. Inhibition results telomere erosion, leading to the subsequent growth arrest followed by senescence or cell death. In this study, we screened a chemical library inhibition human telomerase, identifying three inhibitors. All compounds contained common nitrostyrene moiety conjugated different side chains. One these compounds,...

We have identified an Arabidopsis thaliana cDNA, designated as AtTBP1 , encoding a protein with predicted size of 70.6 kDa that specifically binds to the plant telomeric repeat sequence TTTAGGG. is present single‐copy gene in genome and expressed ubiquitously various organs. has single Myb DNA binding domain at C‐terminus extensive homology other known telomere‐binding proteins. The isolated capable sequence‐specific duplex DNA. These results suggest may play important roles telomere function vivo.

Although several potential telomere binding proteins have been identified in higher plants, their vivo functions are still unknown at the plant level. Both knockout and antisense mutants of RICE TELOMERE BINDING PROTEIN1 (RTBP1) exhibited markedly longer telomeres relative to those wild type, indicating that amount functional RTBP1 is inversely correlated with length. rtbp1 plants displayed progressive severe developmental abnormalities both germination postgermination growth vegetative...

ABSTRACT Telomeres are essential for chromosome integrity and protection, their maintenance requires the ribonucleoprotein enzyme telomerase. Previously, we have shown that human telomerase reverse transcriptase (hTERT) contains a bipartite nuclear localization signal (NLS; residues 222–240) is responsible import, Akt-mediated phosphorylation of residue S227 important efficient import hTERT. Here, show hTERT binds to importin-α proteins through NLS this heterodimer then forms complex with...

ABSTRACT Telomerase is a ribonucleoprotein enzyme that required for the maintenance of telomere repeats. Although overexpression telomerase in normal human somatic cells sufficient to overcome replicative senescence, ability promote tumorigenesis requires additional activities are independent its role extension. Here, we identify proliferation-associated nucleolar antigen 120 (NOL1, also known as NOP2) RNA component (TERC)-binding protein found association with catalytically active...

Telomerase is a unique ribonucleoprotein enzyme that required for continued cell proliferation. To generate catalytically active telomerase, human telomerase reverse transcriptase (hTERT) must translocate to the nucleus and assemble with RNA component of telomerase. The molecular chaperones heat shock protein 90 (Hsp90) p23 maintain hTERT in conformation enables nuclear translocation. However, regulatory role transport remains unclear. In this work, we demonstrate immunophilin FK506-binding...

Scrub typhus is an acute febrile illness caused by Rickettsia tsutsugamushi-induced vasculitis, which common in Asia and the Pacific islands sometimes encountered Western countries because of increased travel economic changes spurred world globalization. Skin rash eschar are typical physical findings on trunk extremities, but endoscopic mucosal have not been described gastrointestinal tract until now. We aimed to describe different characteristics manifestation scrub typhus, ascertain...

Telomere maintenance is essential for the continued proliferation of dividing cells, and implicated in chromosome stability cell immortalization. Telomerase activity allows cells to maintain their telomeric DNA contributes indefinite replicative capacity cancer cells. expressed most but not normal somatic suggesting that telomerase an attractive target chemotherapy. Here we screened a chemical library inhibition human telomerase, identified 2,3,7-trichloro-5-nitroquinoxaline (TNQX) as potent...