Calcineurin dephosphorylates topoisomerase IIβ and regulates the formation of neuronal-activity-induced DNA breaks.

ABSTRACT: Neuronal activity induces topoisomerase IIβ (Top2B) to generate DNA double-strand breaks (DSBs) within the promoters of neuronal early response genes (ERGs) and facilitate their transcription, and yet, the mechanisms that control Top2B-mediated DSB formation are unknown. Here, we report that stimulus-dependent calcium influx through NMDA receptors activates the phosphatase calcineurin to dephosphorylate Top2B at residues S1509 and S1511, which stimulates its DNA cleavage activity and induces it to form DSBs. Exposing mice to a fear conditioning paradigm also triggers Top2B dephosphorylation at S1509 and S1511 in the hippocampus, indicating that calcineurin also regulates Top2B-mediated DSB formation following physiological neuronal activity. Furthermore, calcineurin-Top2B interactions foll

SUBMITTER: Delint-Ramirez I 

PROVIDER: S-EPMC9990814 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature