PRMT5 regulates the homologous recombination DNA repair pathway by controlling the alternative splicing of key epigenetic factors

We found that PRMT5 deletion or inhibition impairs homologous recombination (HR) DNA repair, leading to DNA damage accumulation, p53 activation, cell cycle arrest and cell death through missplicing of KAT5. We show that PRMT5 inhibitors and PARP inhibitors have synergistic effects on human acute leukemia cell lines, demonstrating the advantages of combining targeted epigenetic and non-epigenetic inhibitors. RNA from sorted E14.5 Ter119-/+ mouse fetal liver cells from Vav-cre;PRMT5fl/fl (KO) and PRMT5fl/fl (WT) were subjected to high-throughput RNA sequencing. RNA from sorted LK cells from Mx1-cre;PRMT5fl/fl (KO) and PRMT5fl/fl (WT) collected 7 days after poly(I:C) injections were subjected to high-throughput RNA sequencing.