Browsing by Author "Locatelli, Maëlle"

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    DNA damage reduces heterogeneity and coherence of chromatin motions
    (National Academy of Science, 2022) Locatelli, Maëlle; Lawrimore, Josh; Lin, Hua; Sanaullah, Sarvath; Seitz, Clayton; Segall, Dave; Kefer, Paul; Moreno, Naike Salvador; Lietz, Benton; Anderson, Rebecca; Holmes, Julia; Yuan, Chongli; Holzwarth, George; Bloom, Kerry S.; Liu, Jing; Bonin, Keith; Vidi, Pierre-Alexandre; Physics, School of Science
    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.
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    RAD51 regulates eukaryotic chromatin motions in the absence of DNA damage
    (American Society for Cell Biology, 2024) Maarouf, Amine; Iqbal, Fadil; Sanaullah, Sarvath; Locatelli, Maëlle; Atanasiu, Andrew T.; Kolbin, Daniel; Hommais, Chloé; Mühlemann, Joëlle K.; Bonin, Keith; Bloom, Kerry; Liu, Jing; Vidi, Pierre-Alexandre; Physics, School of Science
    In yeasts and higher eukaryotes, chromatin motions may be tuned to genomic functions, with transcriptional activation and the DNA damage response both leading to profound changes in chromatin dynamics. The RAD51 recombinase is a key mediator of chromatin mobility following DNA damage. As functions of RAD51 beyond DNA repair are being discovered, we asked whether RAD51 modulates chromatin dynamics in the absence of DNA damage and found that inhibition or depletion of RAD51 alters chromatin motions in undamaged cells. Inhibition of RAD51 increased nucleosome clustering. Predictions from polymer models are that chromatin clusters reduce chain mobility and, indeed, we measured reduced motion of individual chromatin loci in cells treated with a RAD51 inhibitor. This effect was conserved in mammalian cells, yeasts, and plant cells. In contrast, RAD51 depletion or inhibition increased global chromatin motions at the microscale. The results uncover a role for RAD51 in regulating local and global chromatin dynamics independently from DNA damage and highlight the importance of considering different physical scales when studying chromatin dynamics.