CTG clade-specific proteins of the RSC chromatin remodeling complex regulate cell cycle progression of a critical priority fungal pathogen, Candida albicans

Abstract

The RSC and the homologous chromatin remodeling complexes are known to regulate cell cycle progression in various organisms, including Saccharomyces cerevisiae, Drosophila, and Homo sapiens. In this work, we characterized the role of two novel CTG clade-specific proteins (Nri1 and Nri2) of the RSC complex in the regulation of cell cycle progression in a critical priority fungal pathogen, Candida albicans. We observed that Nri1, alone or along with Nri2, regulates cell cycle progression at multiple stages. The nri1{Delta}/{Delta} and nri1{Delta}/{Delta} nri2{Delta}/{Delta} mutants exhibited transient cell cycle arrest, defective spindle morphology, and cytokinesis. Transcriptomic analysis supported these mutant phenotypes and indicated a broad role of Nri proteins in the cell cycle. From our results, we conclude that Nri proteins are crucial for C. albicans proliferation and fitness. ImportanceThe composition of the essential RSC chromatin remodeling complex exhibits species-specific divergence, harboring unique subunits with distinct functions. In this study, we report that two fungal CTG clade-specific proteins of the C. albicans RSC complex, namely Nri1 and Nri2 can promote C. albicans fitness through regulating its cell cycle progression at multiple stages. Fitness defect along with stressor sensitivity and differential expression of the genes regulating pathogenesis in the nri mutants indicate potentiality of the Nri proteins as anti-Candida drug targets.