title: Enhanced electrostatic force microscopy reveals higher-order DNA looping mediated by the telomeric protein TRF2.
abstract: 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.
authors: Physics Department, North Carolina State University, Raleigh, North Carolina, NC 27695, USA.
authors: Parminder
authors: P
authors: Kaur
authors: Physics Department, North Carolina State University, Raleigh, North Carolina, NC 27695, USA.
authors: Dong
authors: D
authors: Wu
authors: Physics Department, North Carolina State University, Raleigh, North Carolina, NC 27695, USA.|School of Bioscience and Engineering, South China University of Technology, Guangzhou, Guangdong 510006, P.R. China.
authors: Jiangguo
authors: J
authors: Lin
authors: Physics Department, North Carolina State University, Raleigh, North Carolina, NC 27695, USA.
authors: Preston
authors: P
authors: Countryman
authors: Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599.
authors: Kira C
authors: KC
authors: Bradford
authors: Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599.|Curriculum in Applied Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599.
authors: Dorothy A
authors: DA
authors: Erie
authors: Physics Department, North Carolina State University, Raleigh, North Carolina, NC 27695, USA.
authors: Robert
authors: R
authors: Riehn
authors: Department of Environmental and Occupational Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania 15219, USA.
authors: Patricia L
authors: PL
authors: Opresko
authors: Physics Department, North Carolina State University, Raleigh, North Carolina, NC 27695, USA.
authors: Hong
authors: H
authors: Wang
mesh_terms: D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008853:Microscopy; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000378:metabolism; D009690:Nucleic Acid Conformation; D055672:Static Electricity; D035341:Telomeric Repeat Binding Protein 2 / Q000737:chemistry* / Q000378:metabolism
chemical_list: D046912:Multiprotein Complexes; C504753:TERF2 protein, human; D035341:Telomeric Repeat Binding Protein 2; D004247:DNA