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The telomeric DNA damage response occurs in the absence of chromatin decompaction

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 decomp...

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Autores principales: Vancevska, Aleksandra, Douglass, Kyle M., Pfeiffer, Verena, Manley, Suliana, Lingner, Joachim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5393052/
https://www.ncbi.nlm.nih.gov/pubmed/28381410
http://dx.doi.org/10.1101/gad.294082.116
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author Vancevska, Aleksandra
Douglass, Kyle M.
Pfeiffer, Verena
Manley, Suliana
Lingner, Joachim
author_facet Vancevska, Aleksandra
Douglass, Kyle M.
Pfeiffer, Verena
Manley, Suliana
Lingner, Joachim
author_sort Vancevska, Aleksandra
collection PubMed
description 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.
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spelling pubmed-53930522017-05-01 The telomeric DNA damage response occurs in the absence of chromatin decompaction Vancevska, Aleksandra Douglass, Kyle M. Pfeiffer, Verena Manley, Suliana Lingner, Joachim Genes Dev Research Paper 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. Cold Spring Harbor Laboratory Press 2017-03-15 /pmc/articles/PMC5393052/ /pubmed/28381410 http://dx.doi.org/10.1101/gad.294082.116 Text en © 2017 Vancevska et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by/4.0/ This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
spellingShingle Research Paper
Vancevska, Aleksandra
Douglass, Kyle M.
Pfeiffer, Verena
Manley, Suliana
Lingner, Joachim
The telomeric DNA damage response occurs in the absence of chromatin decompaction
title The telomeric DNA damage response occurs in the absence of chromatin decompaction
title_full The telomeric DNA damage response occurs in the absence of chromatin decompaction
title_fullStr The telomeric DNA damage response occurs in the absence of chromatin decompaction
title_full_unstemmed The telomeric DNA damage response occurs in the absence of chromatin decompaction
title_short The telomeric DNA damage response occurs in the absence of chromatin decompaction
title_sort telomeric dna damage response occurs in the absence of chromatin decompaction
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5393052/
https://www.ncbi.nlm.nih.gov/pubmed/28381410
http://dx.doi.org/10.1101/gad.294082.116
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