21 research outputs found
Inhibition of leukemic cell telomerase activity by antisense phosphorothioate oligodeoxynucleotides
Learning to Manage Shame in School Bullying: Lessons for Restorative Justice Interventions
A bystander cell-based GM-CSF secreting vaccine synergized with a low dose of cyclophosphamide presents therapeutic immune responses against murine hepatocellular carcinoma
Telomere maintenance and length regulation in Trypanosoma brucei
Transcription of telomere proximal variant surface glycoprotein genes is mono-allelic in bloodstream-form Trypanosoma brucei. The terminal DNA sequence at these telomeres consists of tandem T(2)AG(3) repeats, which increase in length by ∼8 bp per cell division balanced by occasional loss of large numbers of repeats. Here we have used targeted chromosome fragmentation to investigate the sequence requirements for telomere formation in T.brucei. Telomere formation is most efficient on tandem T(2)AG(3) repeats, but can also occur on specific templates found within ‘random’ sequence substrates and on G-rich motifs proximal to a double-strand break. Newly formed telomeres are extended faster than other native telomeres, but as the telomere becomes longer the rate of extension declines. Telomere length regulation in T.brucei is discussed in the context of recent results from other cell types
Enhanced electrostatic force microscopy reveals higher-order DNA looping mediated by the telomeric protein TRF2
Shelterin protein TRF2 modulates telomere structures by promoting dsDNA compaction and T-loop formation. Advancement of our understanding of the mechanism underlying TRF2-mediated DNA compaction requires additional information regarding DNA paths in TRF2-DNA complexes. To uncover the location of DNA inside protein-DNA complexes, we recently developed the Dual-Resonance-frequency-Enhanced Electrostatic force Microscopy (DREEM) imaging technique. DREEM imaging shows that in contrast to chromatin with DNA wrapping around histones, large TRF2-DNA complexes (with volumes larger than TRF2 tetramers) compact DNA inside TRF2 with portions of folded DNA appearing at the edge of these complexes. Supporting coarse-grained molecular dynamics simulations uncover the structural requirement and sequential steps during TRF2-mediated DNA compaction and result in folded DNA structures with protruding DNA loops as seen in DREEM imaging. Revealing DNA paths in TRF2 complexes provides new mechanistic insights into structure-function relationships underlying telomere maintenance pathways