How are biological responses designed: some of our take-homes

It is a recurring theme that local biological actions often require large-scale systemic non-local changes in cells and tissues, the design of which is not easily intuitive. We explore this theme using DNA Damage Response (DDR) paradigm in human cells and Drosophila. We uncovered that damaged chromosomes traverse large distances reversibly to repair DNA. Damaged replication forks collapse if the repair remains unabated and the normal repair has inbuilt non-local design to attenuate itself. Interestingly, unrepaired dying cells seem to trigger changes across large distances to provoke additional cellular proliferation, thereby “compensating and renewing” life. Finally I conclude that most of these solutions have their origins in the “system as a whole” rather than from “the parts thereof”.