Rad53 Orchestrates Divergent Pathways Governing Genotoxic Resistance, Morphogenesis, and Virulence in Candida albicans: Mechanistic Decoupling through Overexpression Analysis

In Candida albicans, our prior work characterized Rad53-mediated transcriptional reprogramming based on the RAD53 deletion strain, establishing its canonical DDR functions. However, Rad53 activation dynamically orchestrates cell cycle synchronization and repair coordination during genotoxic challenge.

Investigation of cellular modifications resulting from increased functionality of Rad53 is essential to gain a deeper understanding of the regulatory response of Rad53. To this end, we overexpressed Rad53 revealing its dual regulatory capacity in both stress adaptation and developmental plasticity. Global transcriptomic profiling demonstrated that RAD53 overexpression enhances methyl methanesulfonate (MMS) resistance while paradoxically stimulating filamentous growth, accompanied by upregulation of DNA repair/replication genes (RFA3, POL30) and non-canonical DDR targets including cell wall remodeling factors.