Author: Bandaria JN, Qin P, Berk V, Chu S, Yildiz A
Affiliation: 1Department of Physics, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. 2Department of Physics, University of California, Berkeley, Berkeley, CA 94720, USA. 3Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Physics, Stanford University, Stanford, CA 94305, USA. 4Department of Physics, Stanford University, Stanford, CA 94305, USA. 5Department 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.
Conference/Journal: Cell.
Date published: 2016 Feb 11
Other:
Volume ID: 164 , Issue ID: 4 , Pages: 735-46 , Special Notes: doi: 10.1016/j.cell.2016.01.036. , Word Count: 159
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.
Copyright © 2016 Elsevier Inc. All rights reserved.
PMID: 26871633 [PubMed - in process]