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...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2022-07, Vol.119 (29), p.e2205166119-e2205166119
Main Authors: 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
Format: Article
Language:English
Subjects:
Animals
Biological Sciences
Chromatin
Chromatin - chemistry
Chromatin Assembly and Disassembly
Chromosomes
Conformation
Damage
Deoxyribonucleic acid
Diffractive optics
DNA
DNA Breaks, Double-Stranded
DNA damage
DNA probes
DNA Repair
Eukaryotes
Genomics
Heterogeneity
Lattices
Mammalian cells
Optics
Phase separation
Saccharomyces cerevisiae - genetics
Spatial heterogeneity
Yeasts
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2205166119