Decades of investigation on genomic DNA have brought us deeper insights into its organization within the nucleus and its metabolic mechanisms. This was fueled by the parallel development of experimental techniques and has stimulated model building to simulate genome conformation in agreement with the experimental data. Here, we will discuss our recent discoveries on the chromatin units of DNA replication and DNA damage response. We will highlight their remarkable structural similarities and how both revealed themselves as clusters of nanofocal structures each on the hundred thousand base pair size range corresponding well with chromatin loop sizes. We propose that the function of these two global genomic processes is determined by the loop level organization of chromatin structure with structure dictating function.Abbreviations: 3D-SIM: 3D-structured illumination microscopy; 3C: chromosome conformation capture; DDR: DNA damage response; FISH: fluorescent in situ hybridization; Hi-C: high conformation capture; HiP-HoP: highly predictive heteromorphic polymer model; IOD: inter-origin distance; LAD: lamina associated domain; STED: stimulated emission depletion microscopy; STORM: stochastic optical reconstruction microscopy; SBS: strings and binders switch model; TAD: topologically associated domain.
Keywords: Chromatin structure; DNA repair; DNA replication; DNA structure; chromatin function; high resolution microscopy; polymer modeling.