RecombInsight: Discovery in Mammalian Homologous Recombination DNA Repair

Every time a cell divides, it must repair broken DNA strands with surgical precision, or risk becoming cancerous. This project focuses on the second, poorly understood phase of that repair process—homologous recombination—where the cell matches the broken DNA against an undamaged copy to restore it perfectly. The first phase of this repair is well mapped, but the subsequent steps remain a black box. Without knowing exactly which proteins orchestrate the later stages and how they handle the DNA, researchers cannot fully explain why certain genetic mutations cause premature ageing or dramatically raise cancer risk. This gap also limits the design of therapies that either exploit a cancer cell's faulty repair machinery or deliberately create toxic repair intermediates to kill tumours. This is fundamental science. The project will use chemistry, advanced genome editing, and new imaging techniques to identify the missing cellular factors and track the nucleic acid and protein events at each step. If successful, it will provide the molecular blueprint for a core DNA repair pathway. That blueprint could eventually guide the development of more targeted cancer treatments and clarify the mechanisms behind inherited cancer predisposition syndromes—but the immediate payoff is a deeper understanding of how our cells keep their genetic code intact.