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DNA damage reduces heterogeneity and coherence of chromatin motions
Chromatin motions depend on and may regulate genome functions, in particular the DNA damage response. In yeast, DNA double-strand breaks (DSBs) globally increase chromatin diffusion, whereas in higher eukaryotes the impact of DSBs on chromatin dynamics is more nuanced. We mapped the motions of chrom...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304018/ https://www.ncbi.nlm.nih.gov/pubmed/35858349 http://dx.doi.org/10.1073/pnas.2205166119 |
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author | Locatelli, Maëlle Lawrimore, Josh Lin, Hua Sanaullah, Sarvath Seitz, Clayton Segall, Dave Kefer, Paul Salvador Moreno, Naike Lietz, Benton Anderson, Rebecca Holmes, Julia Yuan, Chongli Holzwarth, George Bloom, Kerry S. Liu, Jing Bonin, Keith Vidi, Pierre-Alexandre |
author_facet | Locatelli, Maëlle Lawrimore, Josh Lin, Hua Sanaullah, Sarvath Seitz, Clayton Segall, Dave Kefer, Paul Salvador Moreno, Naike Lietz, Benton Anderson, Rebecca Holmes, Julia Yuan, Chongli Holzwarth, George Bloom, Kerry S. Liu, Jing Bonin, Keith Vidi, Pierre-Alexandre |
author_sort | Locatelli, Maëlle |
collection | PubMed |
description | Chromatin motions depend on and may regulate genome functions, in particular the DNA damage response. In yeast, DNA double-strand breaks (DSBs) globally increase chromatin diffusion, whereas in higher eukaryotes the impact of DSBs on chromatin dynamics is more nuanced. We mapped the motions of chromatin microdomains in mammalian cells using diffractive optics and photoactivatable chromatin probes and found a high level of spatial heterogeneity. DNA damage reduces heterogeneity and imposes spatially defined shifts in motions: Distal to DNA breaks, chromatin motions are globally reduced, whereas chromatin retains higher mobility at break sites. These effects are driven by context-dependent changes in chromatin compaction. Photoactivated lattices of chromatin microdomains are ideal to quantify microscale coupling of chromatin motion. We measured correlation distances up to 2 µm in the cell nucleus, spanning chromosome territories, and speculate that this correlation distance between chromatin microdomains corresponds to the physical separation of A and B compartments identified in chromosome conformation capture experiments. After DNA damage, chromatin motions become less correlated, a phenomenon driven by phase separation at DSBs. Our data indicate tight spatial control of chromatin motions after genomic insults, which may facilitate repair at the break sites and prevent deleterious contacts of DSBs, thereby reducing the risk of genomic rearrangements. |
format | Online Article Text |
id | pubmed-9304018 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-93040182023-01-12 DNA damage reduces heterogeneity and coherence of chromatin motions Locatelli, Maëlle Lawrimore, Josh Lin, Hua Sanaullah, Sarvath Seitz, Clayton Segall, Dave Kefer, Paul Salvador Moreno, Naike Lietz, Benton Anderson, Rebecca Holmes, Julia Yuan, Chongli Holzwarth, George Bloom, Kerry S. Liu, Jing Bonin, Keith Vidi, Pierre-Alexandre Proc Natl Acad Sci U S A Biological Sciences Chromatin motions depend on and may regulate genome functions, in particular the DNA damage response. In yeast, DNA double-strand breaks (DSBs) globally increase chromatin diffusion, whereas in higher eukaryotes the impact of DSBs on chromatin dynamics is more nuanced. We mapped the motions of chromatin microdomains in mammalian cells using diffractive optics and photoactivatable chromatin probes and found a high level of spatial heterogeneity. DNA damage reduces heterogeneity and imposes spatially defined shifts in motions: Distal to DNA breaks, chromatin motions are globally reduced, whereas chromatin retains higher mobility at break sites. These effects are driven by context-dependent changes in chromatin compaction. Photoactivated lattices of chromatin microdomains are ideal to quantify microscale coupling of chromatin motion. We measured correlation distances up to 2 µm in the cell nucleus, spanning chromosome territories, and speculate that this correlation distance between chromatin microdomains corresponds to the physical separation of A and B compartments identified in chromosome conformation capture experiments. After DNA damage, chromatin motions become less correlated, a phenomenon driven by phase separation at DSBs. Our data indicate tight spatial control of chromatin motions after genomic insults, which may facilitate repair at the break sites and prevent deleterious contacts of DSBs, thereby reducing the risk of genomic rearrangements. National Academy of Sciences 2022-07-12 2022-07-19 /pmc/articles/PMC9304018/ /pubmed/35858349 http://dx.doi.org/10.1073/pnas.2205166119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences Locatelli, Maëlle Lawrimore, Josh Lin, Hua Sanaullah, Sarvath Seitz, Clayton Segall, Dave Kefer, Paul Salvador Moreno, Naike Lietz, Benton Anderson, Rebecca Holmes, Julia Yuan, Chongli Holzwarth, George Bloom, Kerry S. Liu, Jing Bonin, Keith Vidi, Pierre-Alexandre DNA damage reduces heterogeneity and coherence of chromatin motions |
title | DNA damage reduces heterogeneity and coherence of chromatin motions |
title_full | DNA damage reduces heterogeneity and coherence of chromatin motions |
title_fullStr | DNA damage reduces heterogeneity and coherence of chromatin motions |
title_full_unstemmed | DNA damage reduces heterogeneity and coherence of chromatin motions |
title_short | DNA damage reduces heterogeneity and coherence of chromatin motions |
title_sort | dna damage reduces heterogeneity and coherence of chromatin motions |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304018/ https://www.ncbi.nlm.nih.gov/pubmed/35858349 http://dx.doi.org/10.1073/pnas.2205166119 |
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