Candida albicans Snf2 modulates the response to DNA damage by regulating gene expression and uptake of the genotoxic stressors

ABSTRACT The SWI/SNF complex comprising of the catalytic subunit, Snf2, is a key regulator of gene expression and DNA damage repair in eukaryotic cell. Candida albicans Snf2 is known to regulate hyphal formation. In this paper, we have investigated the role of this protein in DNA damage response. We show that Ca Snf2 is required for cell division as deletion of both copies of SNF2 leads to increased duplication time. The mutant cells form clumps with increased chitin and β-glucan deposition on the cell wall. The altered cell wall phenotype leads to reduced uptake of genotoxic stressors leading to increased resistance to both methyl methane sulfonate (MMS) and hydroxyurea (HU). In addition, resistance of Casnf2Δ cells to MMS also appears to be mediated by upregulation of CaRAD9 expression by Ca Fun30, an ATP-dependent chromatin remodeling protein, and Ca Rtt109, a fungal-specific histone acetyltransferase. The response of Casnf2Δ to genotoxic stressors is at variance with the response of Scsnf2Δ mutant, highlighting the differences in DNA damage response/repair pathway between the two organisms. Finally, we show that Casnf2Δ mutants are extremely sensitive to azoles due to downregulation of multi-drug resistance pumps leading to reduced efflux of the drug.