# Yeast as a Platform to Dissect Poly(ADP-Ribose) Polymerase Function from Magnaporthe oryzae and Evaluate PARP Inhibitors

## TL;DR

Researchers used yeast to study a fungal PARP enzyme and test PARP inhibitors, creating a new tool for understanding fungal biology and drug effects.

## Contribution

A novel yeast-based system was developed to study fungal PARP function and evaluate PARP inhibitors in vivo.

## Key findings

- Expression of MoPARP1 in yeast reduced growth, dependent on its catalytic activity.
- PARylation was observed in yeast expressing MoPARP1 but not in catalytic mutants.
- PARP inhibitors rescued yeast growth in a multidrug transporter-deficient background.

## Abstract

Poly(ADP-ribose) polymerases (PARPs) regulate genome maintenance through NAD+-dependent ADP-ribosylation, yet PARP function in fungi remains poorly defined. Here, we reconstituted the activity of the Magnaporthe oryzae PARP1 homolog (MoPARP1) in Saccharomyces cerevisiae, a genetically tractable organism that lacks endogenous PARP enzymes. Upon galactose induction, expression of MoPARP1 reduced yeast growth, whereas a catalytically inactive mutant showed no defect, indicating that the growth phenotype depends on PARP catalytic activity. Consistent with this requirement, PARylation was detected in MoPARP1-expressing yeast cells but not in the catalytic mutant. In a multidrug transporter-deficient background, the PARP inhibitor 3-aminobenzamide and the clinically used PARP inhibitor olaparib rescued the growth of MoPARP1-expressing strains, establishing a framework for inhibitor testing in vivo. Finally, MoPARP1-GFP localized to the nucleus independent of catalytic activity, supporting correct targeting in this heterologous system. Together, these findings establish yeast as a platform to dissect fungal PARP biology and evaluate chemical inhibition.