Mechanisms of DNA Mobilization and Sequestration.

The entire genome becomes mobilized following DNA damage. Understanding the mechanisms that act at the genome level requires that we embrace experimental and computational strategies to capture the behavior of the long-chain DNA polymer, which is the building block for the chromosome. Long-chain polymers exhibit constrained, sub-diffusive motion in the nucleus. Cross-linking proteins, including cohesin and condensin, have a disproportionate effect on genome organization in their ability to stabilize transient interactions. Cross-linking proteins can segregate the genome into sub-domains through polymer-polymer phase separation (PPPS) and can drive the formation of gene clusters through small changes in their binding kinetics. Principles from polymer physics provide a means to unravel the mysteries hidden in the chains of life.