Multi-scale tracking reveals scale-dependent chromatin dynamics after DNA damage

The dynamic organization of genes inside the nucleus is an important determinant for their function. Using fast DNA tracking microscopy in Saccharomyces cerevisiae cells and improved analysis of mean-squared displacements, we quantified DNA motion at time scales ranging from 10 ms to minutes and found that following DNA damage, DNA exhibits distinct subdiffusive regimes. In response to double-strand breaks, chromatin is more mobile at large time scales, but, surprisingly, its mobility is reduced at short time scales. This effect is even more pronounced at the site of damage. Such a pattern of dynamics is consistent with a global increase in chromatin persistence length in response to DNA damage. Scale-dependent nuclear exploration is regulated by the Rad51 repair protein, both at the break and throughout of the genome. We propose a model in which stiffening of the damaged ends by the repair complex, combined with global increased stiffness, act like a “needle in a ball of yarn,” enhancing the ability of the break to traverse the chromatin meshwork.