Decision Making at Protected Replication Forks

Every time a cell copies its DNA, thousands of molecular machines called replication forks race along the chromosomes—and when they stall, a set of protective proteins must step in to stop cellular scissors from snipping the exposed DNA. This protection system is critical: several genes linked to cancer predisposition and developmental disorders encode the very proteins that guard paused forks. Yet researchers do not fully understand where, when, or how this protection works, or how cells decide whether to restart a protected fork or dismantle a broken one. This project will map those decisions at the molecular level. The team will identify which genomic locations most need protection, what triggers the protective response, and how stalled forks signal to recovery machinery. They will also examine how chromatin—the packaging of DNA—is rearranged to allow repair to proceed. This is fundamental science. There is no immediate clinical application. But the process directly suppresses genome instability, a hallmark of cancer. Understanding the molecular logic of fork protection could eventually reveal why certain tumours are vulnerable to particular therapies or become resistant, opening new avenues for treatment design.