science
Neurons migrating in developing brain cortices sustain DNA double-strand breaks that are repaired by non-homologous end-joining
A Nature study finds that neurons migrating through narrow spaces in the developing cerebral and cerebellar cortices sustain extensive DNA double-stranded breaks from mechanical stress. The damage is repaired without cell death, but impaired repair leads to later motor deficits in mice.
NA
neurosciencenews.comAudio version
Tap play to generate a narrated version.
Developing·Limited corroboration so far. This page will refresh as more sources emerge.
Neurons migrating through developing cerebral and cerebellar cortices sustain massive DNA double-stranded breaks caused by mechanical stress during passage through narrow interstitial spaces. @Nature reported that the breaks occur without detectable nuclear envelope rupture, unlike the damage seen in some cancer cells.
Confined migration increases topoisomerase-IIβ covalently bound double-stranded breaks, which are then repaired through non-homologous end-joining.
Genome sequencing showed the breaks tend to occur at transcriptionally inactive regions. Deletion of ligase IV at the start of neuronal migration produced persistent double-stranded break accumulation in cerebellar neurons. The ligase IV deletion triggered moderate transcriptional changes in genes tied to synaptic function, neuronal development, and stress and immune responses.
Mutant mice developed mild motor deficits in later life. The findings show that DNA breaks during normal neuronal migration are repaired through non-homologous end-joining without cell death; only ligase-IV deletion produced persistent breaks and mild motor deficits.
