Scientists at Kyoto University have discovered that neurons routinely break both strands of their own DNA as they migrate through the tightly packed tissue of the developing brain cortex. The damage occurs when the enzyme Topoisomerase IIβ becomes mechanically stuck as newborn nerve cells squeeze through narrow gaps to reach their final positions in the neural circuit.
Rather than being catastrophic, the breaks are repaired within 24 hours using a mechanism called non-homologous end joining. The DNA damage concentrates in inactive regions of the genome, away from genes essential for cell function. The research, published in Nature, was confirmed by engineering mice without the repair enzyme Ligase 4 — the animals developed normally but showed progressive balance and coordination problems as adults.
The findings suggest that every neuron in a healthy brain carries a unique history of controlled damage and repair, potentially contributing to subtle genetic differences between individual nerve cells. Researchers say understanding this process could shed light on why some brain development disorders arise even when no obvious genetic mutation is present.