SRPKs Homolog Dsk1 Regulates Homologous Recombination Repair in Schizosaccharomyces pombe

Serine-arginine protein kinases (SRPKs) play important roles in diverse biological processes such as alternative splicing and cell cycle. However, the functions of SRPKs in DNA damage response remain unclear. Here we characterized the function of SRPKs homolog Dsk1 in regulating DNA repair in the fission yeast Schizosaccharomyces pombe. We demonstrated that Dsk1 defective mutants of loss of the gene, spacer domain, and kinase activity as well as its overexpression mutant exhibited sensitivities of replication stress. Genetic analysis revealed that the loss of dsk1⁺ compromised the efficiency of homologous recombination (HR) repair, and Dsk1 was probably involved in the Rad52- and Rad51-dependent HR repair pathways. Interestingly, Dsk1 translocated into the nucleus upon replication stress and directly interacted with Rad51-mediator Rad52 and phosphorylated Rad52-Ser365 residue. The Rad52-Ser365 phosphorylation-defective mutant was slightly sensitive to replication stress, and the phosphorylation-mimicking mutants exhibited more sensitivities, which were partially correlated with phenotypes of the loss- and gain-of-function of dsk1⁺. This study uncovers a potential HR repair regulator Dsk1 in response to replication stress and implies that its homolog SRPKs may have the conserved targets and functions in higher eukaryotes.

Schizosaccharomyces pombe; DNA damage response; Dsk1; Rad52; SRPK; homologous recombination repair.