Biology of Aging Journal Club - Prion tuning mutagenesis as to enable rapid adaptation - Members +3

Paper Title: Prion-based protein self-assembly tunes mutagenesis to enable rapid adaptation

Summary: Mutations supply the raw material for evolution, yet because most are neutral or deleterious, elevated mutation rates are typically transient. Nonetheless, modeling predicts that a mechanism for heritable but reversible ‘‘mutagenesis switches’’ would be advantageous in some selective contexts. Here, we report that frequent prion-based switching of DNA repair and recombination proteins alters mutagenesis in Saccharomyces *cerevisiae *populations from diverse ecological niches, including the laboratory and clinic, providing adaptive benefits in short-term evolution under strong selective pressure. Self-templating protein assembly alters the activities and interactions of multiple DNA-fidelity factors, reshaping adaptive outcomes while maintaining resilience to genotoxic stress. In the WHO priority pathogen Candida albicans, which diverged from *S. cerevisiae *∼300 million years ago, a key regulator of prion inheritance accelerates the rapid emergence of fluconazole resistance. These findings suggest that protein self-assembly can generate epigenetic memory that tunes genome diversification over multiple generations, enabling rapid adaptation in challenging environments.

https://doi.org/10.1016/j.cell.2026.05.018

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Moderated and hosted by: Byron P. Lee linkedin.com/in/biobitworks cellico.bio Co-founder of Prohm Life (https://prohm.life)

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