Cellular and Pathological Responses to Chromosome DNA Single-Strand Breaks

Every day, each cell in the human body suffers tens of thousands of tiny breaks in one strand of its DNA—and a single, unrepaired break can kill a brain cell. This research aims to explain exactly how cells detect and fix these single-strand breaks, and why the repair process sometimes fails. The team has already discovered a molecular mechanism that turns unrepaired breaks into a trigger for neurodegeneration, offering the first clear explanation of how this damage kills neurons. Without this repair pathway, brain cells die, leading to rare genetic diseases that cause progressive neurological decline. If successful, this work could open new avenues for therapies that prevent or slow neurodegeneration. Because single-strand breaks are the most common form of DNA damage and accumulate with age due to oxidative stress, the findings may extend beyond rare diseases to common age-related conditions such as dementia. This is fundamentally curiosity-driven science, but understanding a core cellular process that goes wrong in ageing has historically led to unexpected clinical breakthroughs—from cancer treatments to drugs that slow degenerative disease.