Local problems and non-local solutions in biological designs: some of our recent 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 normal human cells and Drosophila. We uncover that damaged chromosomes traverse large distances reversibly to repair DNA. Damaged replication forks collapse if the repair remains persistently active where the repair has inbuilt non-local design to attenuate itself. Interestingly, unrepaired dying cells seem to trigger changes across large distances in the tissue-field to provoke additional cellular proliferation, “compensating for death and thereby renewing life”. I illustrate these with examples and argue that most of these biological regulations are based on the “system as a whole” rather than “the parts thereof”.