A molecular understanding of homologous recombination in the context of chromatin

Every time a chromosome breaks, a protein called RAD51 must form a sticky filament that searches through the entire genome to find the matching DNA sequence and stitch the break back together. This process—homologous recombination—is essential for keeping our cells from accumulating lethal or cancer-causing mutations, yet scientists have never seen how RAD51 actually works inside the crowded, tightly packed environment of real chromosomes. The problem is that most studies have stripped away the proteins that normally wrap DNA into chromatin, leaving a gap in understanding how repair happens in living cells. This research will combine two approaches: building purified RAD51 complexes in the lab for structural imaging, and using advanced microscopy to watch RAD51 clusters—called foci—form and disappear inside cells after a break. If successful, this work will reveal the molecular choreography of a fundamental DNA repair machine in its natural context. Because defects in homologous recombination are linked to breast and ovarian cancers—and because cancer cells often disable this pathway—a clearer picture of how RAD51 navigates chromatin could eventually guide strategies to make tumours more vulnerable to existing treatments. For now, this is fundamental science: understanding a core cellular process that has remained stubbornly invisible.