title: No overt nucleosome eviction at deprotected telomeres.
abstract: Dysfunctional telomeres elicit the canonical DNA damage response, which includes the activation of the ATM or ATR kinase signaling pathways and end processing by nonhomologous end joining (NHEJ) or homologous recombination (HR). The cellular response to DNA double-strand breaks has been proposed to involve chromatin remodeling and nucleosome eviction, but whether dysfunctional telomeres undergo chromatin reorganization is not known. Here, we report on the nucleosomal organization of telomeres that have become deprotected through the deletion of the shelterin components TRF2 or POT1. We found no evidence of changes in the nucleosomal organization of the telomeric chromatin or nucleosome eviction near the telomere terminus. An unaltered chromatin structure was observed at telomeres lacking TRF2, which activate the ATM kinase and are a substrate for NHEJ. Similarly, telomeres lacking POT1a and POT1b, which activate the ATR kinase, showed no overt nucleosome eviction. Finally, telomeres lacking TRF2 and Ku70, which are processed by HR, appeared to maintain their original nucleosomal organization. We conclude that ATM signaling, ATR signaling, NHEJ, and HR at deprotected telomeres can take place in the absence of overt nucleosome eviction.
authors.affiliation: Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Wu
authors.forename: Titia
authors.initials: T
authors.lastname: de Lange
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D004249:DNA Damage; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000072200:Ku Autoantigen; D051379:Mice; D018345:Mice, Knockout; D008836:Micrococcal Nuclease / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D000089804:Shelterin Complex; D015398:Signal Transduction / Q000502:physiology; D016615:Telomere / Q000378:metabolism*; D034501:Telomere-Binding Proteins; D035341:Telomeric Repeat Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D009707:Nucleosomes; C507326:POT1 protein, mouse; C512707:POT1b protein, mouse; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D035341:Telomeric Repeat Binding Protein 2; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C576897:Atr protein, mouse; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases; D008836:Micrococcal Nuclease; C000606509:Xrcc6 protein, human; C000606510:Xrcc6 protein, mouse; D000072200:Ku Autoantigen; D011088:DNA Ligases; D000072481:DNA Ligase ATP