Poly(A) site choice and Pol2 CTD Serine-5 status govern lncRNA control of phosphate-responsive <i>tgp1</i> gene expression in fission yeast.

Overview

The repair of mammalian DNA double-strand breaks (DSBs) by classical non-homologous end joining (C-NHEJ) suppresses genomic instability and cancer and is required for development of the immune and nervous system. We hypothesize that proper repair of neural DSBs via C-NHEJ or other end-joining pathways is critical for neural functionality and homeostasis over time and that improper DSB repair could contribute to complex psychiatric and neurodegenerative diseases. Here, we summarize various findings made by our laboratory and others over the years that support this hypothesis. This evidence includes, most recently, our discovery of a set of genes, of which most serve neural functions, that can serve as targets of recurrent DSBs in primary neural stem and progenitor cells. We also present a speculative model, based on our findings, of mechanisms by which recurrent DSBs in neural genes can generate neuronal diversity and contribute to neuropsychiatric disease.