| Autor: |
Locatelli M; Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157., Lawrimore J; Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599., Lin H; Department of Physics, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202., Sanaullah S; Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157., Seitz C; Department of Physics, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202., Segall D; Department of Physics, Wake Forest University, Winston-Salem, NC 27109., Kefer P; Department of Physics, Wake Forest University, Winston-Salem, NC 27109., Salvador Moreno N; Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157., Lietz B; Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157., Anderson R; Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157., Holmes J; Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157., Yuan C; Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN 47907., Holzwarth G; Department of Physics, Wake Forest University, Winston-Salem, NC 27109., Bloom KS; Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599., Liu J; Department of Physics, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202.; Melvin and Bren Simon Comprehensive Cancer Center, Indiana University, Indianapolis, IN 46202.; Center for Computational Biology and Bioinformatics, Indiana University, Indianapolis, IN 46202., Bonin K; Department of Physics, Wake Forest University, Winston-Salem, NC 27109.; Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC 27157., Vidi PA; Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157.; Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC 27157.; Laboratoire InGenO, Institut de Cancérologie de l'Ouest, 49055 Angers, France. |
| Abstrakt: |
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. |
