Maintaining Genome Stability: Genetic Recombination, DNA Repair and Chromosome Biology Initiated by DNA Misfolding

Every time a human cell divides, it must perfectly copy six billion DNA letters and pull the two copies to opposite ends of the cell—a process that, when it fails, drives cancer and genetic disease. This research tackles two fundamental questions about that process. First, how do cells repair broken DNA without introducing errors? The team will deliberately break chromosomes using DNA palindromes and repetitive sequences, then watch the repair happen under a microscope and at the level of individual DNA molecules. Second, how do cells physically separate the two new chromosomes during division? To find out, the researchers will create mutant cells that position their chromosomes incorrectly, then identify the protein machinery responsible for the failure. This is fundamental science. It will not produce a drug or a diagnostic test tomorrow. But the mechanisms at work here—DNA repair and chromosome segregation—are the same ones that go wrong in most cancers and in many inherited disorders. Understanding them at the molecular level is a prerequisite for knowing why those failures happen and, eventually, how to prevent or correct them. Past discoveries in this field have already yielded chemotherapy drugs and prenatal screening tests.