Fun30 chromatin remodeler helps in dealing with torsional stress and camptothecin-induced DNA damage

Abstract

Fun30 is an ATP-dependent chromatin remodeler in budding yeast that is involved in cellular processes important for maintaining genomic stability such as gene silencing and DNA damage repair. Cells lacking Fun30 are moderately sensitive to the topoisomerase inhibitor camptothecin and exhibit a delay in cell cycle progression in the presence of camptothecin. Here, we show that Fun30 is required to cope with torsional stress in the absence of Top1. Moreover, we show through genetic studies that Fun30 acts in a parallel pathway to Mus81 endonuclease but is epistatic to Tdp1 phosphodiesterase and Rad1 endonuclease in the repair of camptothecin-induced DNA damage. More importantly, we show that DNA damage sensitivity of Fun30 deficient cells is enhanced in the absence of RNase H enzymes that remove RNA:DNA hybrids. We believe that chromatin remodeling by Fun30 may be important in dealing with torsional stress and camptothecin-induced DNA damage.

Keywords: DNA repair; Fun30; camptothecin; chromatin remodeler; homologous recombination; torsional stress.