Grant: Operating Grant

Our life starts as the gametes of our parents fuse into a single cell. The progeny of this cell will divide thousands of times as we develop and grow, transferring from mother to daughter cells the instructions to make us at every cell division. These instructions are coded in molecules of DNA, and a large molecular machine, called the replisome, works in our cells to duplicate DNA through the coordinated activity of numerous protein factors. Failure to transmit genetic information reliably can lead to the generation of genetic diseases, like cancer, and this is why replisome has evolved to have outstanding fidelity at copying DNA and is capable of linking together millions of DNA building blocks without introducing a single mistake. Despite its importance, we still lack key information on the molecular architecture of replisome and on how do its components function together. In this work, we propose to exploit recent advances in genetics and microscopy in order to observe replisome as it works in live cells. This is a novel approach that, in contrast to other methods used in the past, will allow us to extract the information while preserving cells alive, bringing us closer to understand how this cellular processes really happen. We aim to obtain important information on the regulation, composition and function of replisome. Furthering our knowledge on DNA replication will eventually explain its link to the generation and progression of genetic diseases and will help in developing treatments for them.