DNA damage induces differentiated response of chromatin motion across temporal scales.

Abstract

Movement of chromatin in human cells is complicated. Emerging evidence from single particle tracking (SPT) of chromatin loci have shown that chromatin motion is highly dependent on molecular size and time lag in SPT measurements. The physical foundations behind these observations are unclear. Most theoretical studies of chromatin dynamics that are based on the polymer model fail to explain this behavior. We have proposed a single molecule imaging strategy that can track the dynamics of the single nucleosomes in the human cell. By conducting the temporal-varying imaging, we have identified that the measured chromatin motion includes two types of movements, i.e. the fast local fluctuation of the nucleosome, and the slow chromatin chain movement. This conclusion was further validated by the theoretical modeling through ChromoShake. Furthermore, we investigated the response of nucleosome dynamics to the DNA damage. Interestingly, the bleomycin induces the accelerated motion of nucleosomes at short time scale (interval ∼ 30 ms), while the motion of nucleosomes at long time scale (interval ∼seconds) is reduced. This disparity discloses that the DNA damage accelerates the local chromatin motion, while slows down the chromatin chain movement.