Modular Architecture of the SAGA Complex Governs Stress Adaptation, Morphogenesis, and Histone Acetylation in Candida albicans

Abstract

The SAGA complex is a conserved, multifunctional transcriptional co-activator known for its roles in chromatin modification and transcriptional regulation. While SAGA has been extensively characterized in Saccharomyces cerevisiae and metazoans, its modular organization and functional significance in the major human fungal pathogen Candida albicans remain poorly understood. Through bioinformatic analyses, we found that SAGA subunits are conserved in C. albicans. Genetic disruption of the histone acetyltransferase (HAT; GCN5, ADA2), structural (SPT; SPT7, SPT20, TAF12L), and TATA-binding protein interaction (TBP-interaction; SPT3, SPT8) modules leads to impaired growth under oxidative, metal, and antifungal stress conditions and causes severe defects in filamentation. In contrast, deletion of the deubiquitination (DUB) module components UBP8 and SUS1 results in minimal phenotypic consequences. Strikingly, loss of SGF73, a structural component linking the DUB module to the SAGA core, produces pronounced defects in stress conditions and filamentation, phenocopying SPT3 and SPT8 mutants. Consistent with these observations, filamentation-associated genes are significantly upregulated in SGF73, SPT3 and SPT8 mutants. Notably, these mutants also exhibit elevated global levels of histone H3 lysine-9 acetylation (H3K9ac), suggesting a critical role for SGF73-mediated SAGA integrity in coordinating chromatin acetylation with transcriptional programs governing stress responses and filamentation in C. albicans.