title: Isolation of chromatin from dysfunctional telomeres reveals an important role for Ring1b in NHEJ-mediated chromosome fusions.
abstract: When telomeres become critically short, DNA damage response factors are recruited at chromosome ends, initiating a cellular response to DNA damage. We performed proteomic isolation of chromatin fragments (PICh) in order to define changes in chromatin composition that occur upon onset of acute telomere dysfunction triggered by depletion of the telomere-associated factor TRF2. This unbiased purification of telomere-associated proteins in functional or dysfunctional conditions revealed the dynamic changes in chromatin composition that take place at telomeres upon DNA damage induction. On the basis of our results, we describe a critical role for the polycomb group protein Ring1b in nonhomologous end-joining (NHEJ)-mediated end-to-end chromosome fusions. We show that cells with reduced levels of Ring1b have a reduced ability to repair uncapped telomeric chromatin. Our data represent an unbiased isolation of chromatin undergoing DNA damage and are a valuable resource to map the changes in chromatin composition in response to DNA damage activation.
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bartocci
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Jolene K
authors.initials: JK
authors.lastname: Diedrich
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Iliana
authors.initials: I
authors.lastname: Ouzounov
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, 20146 Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Piunti
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, 20146 Milan, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Pasini
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: edenchi@scripps.edu.
authors.forename: Eros
authors.initials: E
authors.lastname: Lazzerini Denchi
mesh_terms: D002843:Chromatin / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D004249:DNA Damage; D059766:DNA End-Joining Repair; D006801:Humans; D063150:Polycomb Repressive Complex 1 / Q000235:genetics* / Q000378:metabolism; D016615:Telomere / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D002843:Chromatin; D063150:Polycomb Repressive Complex 1; C489841:RNF2 protein, human