Evolutionary Divergence in DNA Damage Responses among Fungi

Area of Science:

• Molecular Biology
• Genetics
• Evolutionary Biology

Background:

• Cell cycle checkpoints and DNA repair are crucial for genome integrity and are generally conserved across eukaryotes.
• In yeast (Saccharomyces cerevisiae) and humans, DNA damage triggers checkpoint kinases like Rad53p (human homolog Chk2) to arrest the cell cycle and induce DNA repair genes.

Purpose of the Study:

• To investigate the evolutionary diversity of DNA damage response networks in fungi.
• To compare the DNA damage response of Candida glabrata to Saccharomyces cerevisiae.

Main Methods:

• Comparative analysis of DNA damage response pathways.
• Examination of Rad53p activation and downstream gene transcription in response to DNA damage.

Main Results:

• Candida glabrata exhibits reduced activation of the checkpoint kinase Rad53p upon DNA damage compared to Saccharomyces cerevisiae.
• Key genome maintenance genes, including DNA polymerases, are transcriptionally downregulated in C. glabrata following DNA damage.
• This downregulation correlates with increased rates of mitotic failure and cell death in C. glabrata.

Conclusions:

• The DNA damage response network shows significant evolutionary variation among fungi.
• Reduced checkpoint activation and downstream gene expression in C. glabrata contribute to its genomic instability and pathogenicity.