Abstract

Co-authors: Andrew Seeber (Friedrich Miescher Institute for Biomedical Research), Susan M. Gasser (Friedrich Miescher Institute for Biomedical Research), David Holcman (Ecole Normale Supérieure)

Double-strand break (DSB) repair by homologous recombination (HR) requires an efficient and timely search for a homologous template. Here we developed a statistical method of analysis based on single-particle trajectory data which allows us to extract forces acting on chromatin at DSBs. We can differentiate between extrinsic forces from the actin cytoskeleton and intrinsic alterations on the nucleosomal level at the cleaved MAT locus in budding yeast. Using polymer models we show that reduced tethering forces lead to local decondensation near DSBs, which reduces the mean first encounter time by two orders of magnitude. Local decondensation, likely stems from loss of internal mechanical constraints and a local redistribution of nucleosomes that depends on chromatin remodelers. Simulations verify that local changes in inter-nucleosomal contacts near DSBs would shorten drastically the time required for a long-range homology search.