Orateur
Description
Maelle Locatelli2, Chloé Hommais1, Fadil Iqbal3, Keith Bonin4, Kerry Bloom2, Jing Liu3, and Pierre-Alexandre Vidi1
1 Institut de Cancérologie de l’Ouest, Angers, France
2 Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, USA
3 Department of Physics, Purdue University, West-Lafayette, USA
4 Department of Physics, Wake Forest University, Winston-Salem, USA
Chromatin mobility is influenced by and may regulate genome functions, including the DNA damage response. We mapped the motions of chromatin microdomains in mammalian cells using structured illumination of photoactivatable histone probes and found high levels of heterogeneity between cells and within individual cell nuclei. DNA damage reduces heterogeneity and alters chromatin dynamics: motions are globally reduced but higher mobility is retained at break sites. These effects are driven by context-dependent changes in chromatin compaction. Using an X-ray system integrated to the microscope, we detected a rapid decrease in global chromatin motions, occurring within minutes following break induction. Measurements with nuclear nanoparticles show that nucleoplasmic macromolecule dynamics are also rapidly impacted by DNA damage, with likely consequences on chromatin accessibility. Irradiating cells on the microscope enables us to evaluate DNA damage outcomes relative to chromatin dynamics at the single cell level. The results indicate that the capacity of cells to process radiation-induced DNA damage as well as DNA repair outcomes depend on chromatin mobility. Overall, our data show that chromatin motions are finely tuned after genomic insults and that chromatin motions influence DNA repair.
