The putative error prone polymerase REV1 mediates DNA damage and drug resistance in Candida albicans

Area of Science:

• Microbiology
• Molecular Biology
• Genetics

Background:

• Antimicrobial use can induce DNA damage, promoting mutations and antimicrobial resistance, a phenomenon well-studied in bacteria but less so in fungi.
• The fungal pathogen *Candida albicans* is a significant cause of opportunistic infections, and understanding its resistance mechanisms is crucial.

Purpose of the Study:

• To investigate DNA damage induced by antifungal agents in *Candida albicans*.
• To explore the role of the error-prone polymerase REV1 in the DNA damage response, mutagenesis, and antifungal resistance evolution in *C. albicans*.

Main Methods:

• Monitoring DNA damage in *C. albicans* after exposure to antifungal drugs.
• Analyzing the upregulation of DNA repair factors, including putative error-prone polymerases.
• Gene deletion studies focusing on *REV1* and assessing sensitivity to DNA damage and mutation rates.
• Investigating the impact of *REV1* deletion on the uncharacterized protein Shm1.

Main Results:

• Common antifungal drugs induce DNA damage in *C. albicans*.
• Antifungal treatment leads to the upregulation of transcripts for error-prone polymerases and related factors.
• Deletion of *REV1* increases sensitivity to DNA damage but paradoxically enhances mutation acquisition and antifungal resistance evolution.
• Loss of *REV1* results in depletion of the protein Shm1, which is implicated in fungal mutagenesis.

Conclusions:

• Antifungal-induced DNA damage and repair pathways contribute to the evolution of antifungal resistance in *C. albicans*.
• The error-prone polymerase REV1 and the protein Shm1 play complex roles in the DNA damage response and mutagenesis, impacting antifungal resistance.
• This study provides novel insights into the mechanisms underlying antifungal drug resistance in a key fungal pathogen.