A5047597981- Telomeres, Telomerase, and Senescence
- DNA Repair Mechanisms
- Genetics, Aging, and Longevity in Model Organisms
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- Advanced biosensing and bioanalysis techniques
- Mitochondrial Function and Pathology
- Chromosomal and Genetic Variations
- Microtubule and mitosis dynamics
- Cancer-related Molecular Pathways
- Spaceflight effects on biology
- interferon and immune responses
- Pluripotent Stem Cells Research
- RNA Interference and Gene Delivery
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Molecular Biology Techniques and Applications
- PARP inhibition in cancer therapy
- Heat shock proteins research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cancer Research and Treatments
- Virus-based gene therapy research
- Epigenetics and DNA Methylation
- Microplastics and Plastic Pollution
- Acute Myeloid Leukemia Research
Salk Institute for Biological Studies
2015-2024
La Jolla Alcohol Research
2012-2023
Rockefeller University
1999-2009
Vienna Biocenter
1998
University of Vienna
1996-1997
Although broken chromosomes can induce apoptosis, natural chromosome ends (telomeres) do not trigger this response. It is shown that suppression of apoptosis involves the telomeric-repeat binding factor 2 (TRF2). Inhibition TRF2 resulted in a subset mammalian cell types. The response was mediated by p53 and ATM (ataxia telangiectasia mutated) kinase, consistent with activation DNA damage checkpoint. Apoptosis due to rupture dicentric formed end-to-end fusion, indicating telomeres lacking...
Primary human cells in culture invariably stop dividing and enter a state of growth arrest called replicative senescence. This transition is induced by programmed telomere shortening, but the underlying mechanisms are unclear. Here, we report that overexpression TRF2, telomeric DNA binding protein, increased rate shortening primary without accelerating TRF2 reduced senescence setpoint, defined as length at senescence, from 7 to 4 kilobases. protected critically short telomeres fusion...
Cells from Werner syndrome patients are characterized by slow growth rates, premature senescence, accelerated telomere shortening and genome instability. The is caused the loss of RecQ helicase WRN, but underlying molecular mechanism unclear. Here we report that cells lacking WRN exhibit deletion telomeres single sister chromatids. Only replicated lagging strand synthesis were affected, prevention individual was dependent on activity WRN. Telomere could be counteracted telomerase activity....
The telomeric protein TRF2 is required to prevent mammalian telomeres from activating DNA damage checkpoints. Here we show that overexpression of affects the response ATM kinase damage. Overexpression abrogated cell cycle arrest after ionizing radiation and diminished several other readouts response, including phosphorylation Nbs1, induction p53, upregulation p53 targets. inhibited autophosphorylation on S1981, an early step in activation this kinase. A region containing S1981 was found...
Abstract Cancers arise through the accumulation of genetic and epigenetic alterations that enable cells to evade telomere-based proliferative barriers achieve immortality. One such barrier is replicative crisis—an autophagy-dependent program eliminates checkpoint-deficient with unstable telomeres other cancer-relevant chromosomal aberrations 1,2 . However, little known about molecular events regulate onset this important tumour-suppressive barrier. Here we identified innate immune sensor...
Abstract Telomeres are the protective nucleoprotein structures at end of linear eukaryotic chromosomes. Telomeres’ repetitive nature and length have traditionally challenged precise assessment composition individual human telomeres. Here, we present Telo-seq to resolve bulk, chromosome arm-specific allele-specific telomere lengths using Oxford Nanopore Technologies’ native long-read sequencing. resolves shortening in five population doubling increments reveals intrasample, arm-specific,...
Within the region around 150 bp upstream of initiation codon, which was previously shown to suffice for growth-regulated expression, murine thymidine kinase gene carries a single binding site transcription factor Sp1; about 10 downstream this site, there is motif E2F. The latter protein appears be responsible growth regulation promoter. Mutational inactivation either Sp1 or E2F almost completely abolishes promoter activity, suggesting that two factors interact directly in delivering an...
Werner syndrome (WS) is a rare human premature aging disease caused by mutations in the gene encoding RecQ helicase WRN. In addition to features, this disorder marked genomic instability, associated with an elevated incidence of cancer. Several lines evidence suggest that telomere dysfunction phenotype syndrome; however, origin instability observed WS cells and reason for high cancer have not been established. We previously proposed WRN activity was necessary prevent dramatic loss during DNA...
Werner's syndrome (WS) and Bloom's (BS) are cancer predisposition disorders caused by loss of function the RecQ helicases WRN or BLM, respectively. BS WS characterized replication defects, hyperrecombination events chromosomal aberrations, which hallmarks cancer. Inefficient G-rich telomeric strand contributes to chromosome aberrations in cells, demonstrating a link between WRN, telomeres genomic stability. Herein, we provide evidence that BLM also chromosome-end maintenance. Telomere...
A protein to trim too-long telomeres Telomeres cap the ends of linear eukaryotic chromosomes. They consist multiple copies short DNA repeats. The length is important genome stability; if they become too short, individuals can prone cancer and premature aging. Li et al. discovered a protein, TZAP (telomeric zinc finger–associated protein), which instead prevents from becoming long (see Perspective by Lossaint Lingner). binds directly telomeric repeats, competing with shelterin complex. It...