Ubiquitylation pathways controlling the end of chromosome replication

Every time a human cell divides, it must destroy the molecular machine that just finished copying its chromosomes—and this project aims to find out exactly how that destruction is triggered. The replisome is the protein complex that duplicates DNA before cell division. If it lingers too long, cells can end up with extra or damaged genetic material, a hallmark of cancer. Researchers know the replisome is dismantled by a process called ubiquitylation, which tags proteins for disposal, but the specific enzymes that apply those tags remain unidentified. This project will hunt for those enzymes and determine how the cell ensures they act only after replication is complete, not a moment sooner. This is fundamental science. There is no immediate clinical application. But understanding how cells safely shut down the replisome could reveal why that shutdown fails in cancer cells, where uncontrolled replication drives tumour growth. In the longer term, drugs that mimic or block this destruction process might offer new ways to stop cancer cells from dividing. Past discoveries in ubiquitylation have already led to cancer therapies, such as lenalidomide, which works by hijacking the cell’s own protein-tagging machinery.