title: Shelterin Protects Chromosome Ends by Compacting Telomeric Chromatin.
abstract: Telomeres, repetitive DNA sequences at chromosome ends, are shielded against the DNA damage response (DDR) by the shelterin complex. To understand how shelterin protects telomere ends, we investigated the structural organization of telomeric chromatin in human cells using super-resolution microscopy. We found that telomeres form compact globular structures through a complex network of interactions between shelterin subunits and telomeric DNA, but not by DNA methylation, histone deacetylation, or histone trimethylation at telomeres and subtelomeric regions. Mutations that abrogate shelterin assembly or removal of individual subunits from telomeres cause up to a 10-fold increase in telomere volume. Decompacted telomeres accumulate DDR signals and become more accessible to telomere-associated proteins. Recompaction of telomeric chromatin using an orthogonal method displaces DDR signals from telomeres. These results reveal the chromatin remodeling activity of shelterin and demonstrate that shelterin-mediated compaction of telomeric chromatin provides robust protection of chromosome ends against the DDR machinery.
authors.affiliation: Department of Physics, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Jigar N
authors.initials: JN
authors.lastname: Bandaria
authors.affiliation: Department of Physics, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Peiwu
authors.initials: P
authors.lastname: Qin
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Physics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Veysel
authors.initials: V
authors.lastname: Berk
authors.affiliation: Department of Physics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Chu
authors.affiliation: Department of Physics, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: yildiz@berkeley.edu.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Yildiz
mesh_terms: D042002:Chromatin Assembly and Disassembly; D004249:DNA Damage; D004260:DNA Repair; D006367:HeLa Cells; D006801:Humans; D055503:Protein Multimerization; D000089804:Shelterin Complex; D035182:TATA Box Binding Protein-Like Proteins / Q000378:metabolism; D016615:Telomere / Q000378:metabolism; D034501:Telomere-Binding Proteins / Q000378:metabolism*; D035341:Telomeric Repeat Binding Protein 2 / Q000378:metabolism
chemical_list: C440849:POT1 protein, human; D000089804:Shelterin Complex; D035182:TATA Box Binding Protein-Like Proteins; C441409:TBPL1 protein, human; C504753:TERF2 protein, human; C440868:TINF2 protein, human; D034501:Telomere-Binding Proteins; D035341:Telomeric Repeat Binding Protein 2