Fission yeast Srr1 and Skb1 promote isochromosome formation at the centromere

• Published in: Communications biology 2023-05, Vol.6 (1), p.551-551, Article 551
• Main Authors: Mongia, Piyusha, Toyofuku, Naoko, Pan, Ziyi, Xu, Ran, Kinoshita, Yakumo, Oki, Keitaro, Takahashi, Hiroki, Ogura, Yoshitoshi, Hayashi, Tetsuya, Nakagawa, Takuro
• Format: Article
• Language: English
• Subjects: 13; 13/1; 14; 14/35; 14/63; 38; 45/23; 45/77; 631/208/211; 631/337/103/90; 631/337/1427/2190; 631/337/149; 64; 82; Arginine; Biology; Biomedical and Life Sciences; Cell cycle; Centromere - genetics; Centromere - metabolism; Centromeres; Chromosome rearrangements; Cytology; DNA damage; DNA methylation; DNA repair; Genetic analysis; Genomes; Homologous Recombination; Humans; Isochromosomes; Life Sciences; Methyltransferases - genetics; Protein arginine methyltransferase; Protein Kinases - genetics; Protein-Arginine N-Methyltransferases - metabolism; Rad52 protein; Recombinase; RNA-Binding Proteins - metabolism; Schizosaccharomyces - genetics; Schizosaccharomyces - metabolism; Schizosaccharomyces pombe Proteins - genetics; Schizosaccharomyces pombe Proteins - metabolism; Yeast
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-023-04925-9

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 that srr1 and skb1 mutations reduce isochromosome formation mediated by centromere inverted repeats. srr1 increases DNA damage sensitivity in rad51 cells but does not abolish checkpoint response, suggesting that Srr1 promotes Rad51-independent DNA repair. srr1 and rad52 additively, while skb1 and rad52 epistatically reduce GCRs. Unlike srr1 or rad52 , skb1 does 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. Srr1/Ber1 containing the SRR1-like domain and Skb1 the human protein arginine methyltransferase 5 (PRMT5) homolog cause gross chromosomal rearrangements at centromeres in the absence of Rad51 recombinase.