The role of novel genes rrp1+ and rrp2+ in the repair of DNA damage in Schizosaccharomyces pombe

We identified two predicted proteins in Schizosaccharomyces pombe, Rrp1 (SPAC17A2.12) and Rrp2 (SPBC23E6.02) that share 34% and 36% similarity to Saccharomyces cerevisiae Ris1p, respectively. Ris1p is a DNA-dependent ATP-ase involved in gene silencing and DNA repair. Rrp1 and Rrp2 also share similarity with S. cerevisiae Rad5 and S. pombe Rad8, containing SNF2-N, RING finger and Helicase-C domains. To investigate the function of the Rrp proteins, we studied the DNA damage sensitivities and genetic interactions of null mutants with known DNA repair mutants. Single Delta rrp1 and Delta rrp2 mutants were not sensitive to CPT, 4NQO, CDPP, MMS, HU, UV or IR. The double mutants Delta rrp1 Delta rhp51 and Delta rrp2 Delta rhp51 plus the triple Delta rrp1 Delta rrp2 Delta rhp51 mutant did not display significant additional sensitivity. However, the double mutants Delta rrp1 Delta rhp57 and Delta rrp2 Delta rhp57 were significantly more sensitive to MMS, CPT, HU and IR than the Delta rhp57 single mutant. The checkpoint response in these strains was functional. In S. pombe, Rhp55/57 acts in parallel with a second mediator complex, Swi5/Sfr1, to facilitate Rhp51-dependent DNA repair. Delta rrp1 Delta sfr1 and Delta rrp2 Delta sfr1 double mutants did not show significant additional sensitivity, suggesting a function for Rrp proteins in the Swi5/Sfr1 pathway of DSB repair. Consistent with this, Delta rrp1 Delta rhp57 and Delta rrp2 Delta rhp57 mutants, but not Delta rrp1 Delta sfr1 or Delta rrp2 Delta sfr1 double mutants, exhibited slow growth and aberrations in cell and nuclear morphology that are typical of Delta rhp51. (C) 2008 Elsevier B.V. All rights reserved.