Rad51 maintains genome integrity, whereas Rad52 causes non-canonical homologous recombination leading to gross chromosomal rearrangements (GCRs). Here we find that fission yeast Srr1/Ber1 and Skb1/PRMT5 promote GCRs at centromeres. Genetic and physical analyses show thatsrr1andskb1mutations reduce isochromosome formation mediated by centromere inverted repeats.srr1increases DNA damage sensitivity inrad51cells but does not abolish checkpoint response, suggesting that Srr1 promotes Rad51-independent DNA repair.srr1andrad52additively, whileskb1andrad52epistatically reduce GCRs. Unlikesrr1orrad52,skb1does not increase damage sensitivity. Skb1 regulates cell morphology and cell cycle with Slf1 and Pom1, respectively, but neither Slf1 nor Pom1 causes GCRs. Mutating conserved residues in the arginine methyltransferase domain of Skb1 greatly reduces GCRs. These results suggest that, through arginine methylation, Skb1 forms aberrant DNA structures leading to Rad52-dependent GCRs. This study has uncovered roles for Srr1 and Skb1 in GCRs at centromeres.