DNA double-strand breaks as drivers of neural genomic change, function, and disease

Abstract

Early work from about two decades ago implicated DNA double-strand break (DSB) formation and repair in neuronal development. Findings emerging from recent studies of DSBs in proliferating neural progenitors and in mature, non-dividing neurons suggest important roles of DSBs in brain physiology, aging, cancer, psychiatric and neurodegenerative disorders. We provide an overview of some findings and speculate on what may lie ahead.

Keywords: Copy number variations; DNA double-strand breaks; DNA repair; DNA replication; Exon shuffling; Genomic instability; Neural stem and progenitor cells; Neurodevelopment; Neurons; Non-homologous end joining; Somatic mosaicism; Transcription.