SET7-mediated TIP60 methylation is essential for DNA double-strand break repair

Abstract

The repair of DNA double-strand breaks (DSBs) by homologousrecombination (HR) is crucial for maintaining genomic integrityand is involved in numerous fundamental biological processes. Post-translational modifications by proteins play an importantrole in regulating DNA repair. Here, we report that the methyltransferaseSET7 regulates HR-mediated DSB repair by methylatingTIP60, a histone acetyltransferase and tumor suppressorinvolved in gene expression and protein stability. We showthat SET7 targets TIP60 for methylation at K137, which facilitatesDSB repair by promoting HR and determines cell viabilityagainst DNA damage. Interestingly, TIP60 demethylation is catalyzedby LSD1, which affects HR efficiency. Taken together,our findings reveal the importance of TIP60 methylation statusby SET7 and LSD1 in the DSB repair pathway.