Enzymatic and Structural Roles of Candida albicans Rev1 in DNA Damage Response and Disseminated Candidiasis

Area of Science:

• Molecular Biology
• Genetics
• Mycology

Background:

• Translesion DNA synthesis (TLS) is vital for replicating damaged DNA, ensuring genome stability.
• Rev1, a Y-family DNA polymerase, collaborates with Polζ in TLS, but its catalytic role is debated.
• Candida albicans is an opportunistic fungal pathogen causing severe infections.

Purpose of the Study:

• To characterize the function of Rev1 in Candida albicans, focusing on its role in TLS and virulence.
• To investigate the importance of Rev1's catalytic activity and protein interactions in DNA damage tolerance.
• To assess the contribution of CaRev1 to systemic candidiasis.

Main Methods:

• Genetic analysis of Rev1 mutants under various DNA-damaging conditions.
• Biochemical assays to study Rev1's interactions with PCNA and Polζ.
• DNA damage recovery and mutagenesis assays.
• Animal studies to evaluate CaRev1's role in systemic candidiasis.

Main Results:

• Rev1's catalytic activity is dispensable for most lesion bypasses in C. albicans, except for 4-NQO-induced lesions.
• Interactions between Rev1's BRCT domain, C-terminal domain, PCNA, and Polζ are essential for TLS.
• Domain-specific roles of Rev1 in DNA damage response and mutagenesis were confirmed.
• CaRev1 was found to be dispensable for the development of systemic candidiasis in animal models.

Conclusions:

• Rev1's function in C. albicans TLS is primarily mediated by protein-protein interactions rather than its catalytic activity.
• The specific roles of Rev1 domains are lesion-dependent.
• Other TLS DNA polymerases may compensate for CaRev1 during host infection.
• CaRev1 is not essential for C. albicans pathogenesis despite its importance in DNA repair.