title: The telomeric DNA damage response occurs in the absence of chromatin decompaction.
abstract: Telomeres are specialized nucleoprotein structures that protect chromosome ends from DNA damage response (DDR) and DNA rearrangements. The telomeric shelterin protein TRF2 suppresses the DDR, and this function has been attributed to its abilities to trigger t-loop formation or prevent massive decompaction and loss of density of telomeric chromatin. Here, we applied stochastic optical reconstruction microscopy (STORM) to measure the sizes and shapes of functional human telomeres of different lengths and dysfunctional telomeres that elicit a DDR. Telomeres have an ovoid appearance with considerable plasticity in shape. Examination of many telomeres demonstrated that depletion of TRF2, TRF1, or both affected the sizes of only a small subset of telomeres. Costaining of telomeres with DDR markers further revealed that the majority of DDR signaling telomeres retained a normal size. Thus, DDR signaling at telomeres does not require decompaction. We propose that telomeres are monitored by the DDR machinery in the absence of telomere expansion and that the DDR is triggered by changes at the molecular level in structure and protein composition.
authors.affiliation: Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Vancevska
authors.affiliation: Institute of Physics, Laboratory of Experimental Biophysics, EPFL, 1015 Lausanne, Switzerland.
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Douglass
authors.affiliation: Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Verena
authors.initials: V
authors.lastname: Pfeiffer
authors.affiliation: Institute of Physics, Laboratory of Experimental Biophysics, EPFL, 1015 Lausanne, Switzerland.
authors.forename: Suliana
authors.initials: S
authors.lastname: Manley
authors.affiliation: Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Joachim
authors.initials: J
authors.lastname: Lingner
mesh_terms: D002843:Chromatin / Q000502:physiology; D004249:DNA Damage; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008856:Microscopy, Fluorescence; D016615:Telomere / Q000648:ultrastructure*; D035321:Telomeric Repeat Binding Protein 1 / Q000032:analysis / Q000276:immunology / Q000502:physiology; D035341:Telomeric Repeat Binding Protein 2 / Q000502:physiology
chemical_list: D002843:Chromatin; C504753:TERF2 protein, human; D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2
keywords: DNA damage response; STORM; chromatin compaction; telomeres