Work

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

Year: 2026

Type: article

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.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms27041901

Authors: Rachel E. Kalicharan, Nalleli Payne, Jessie Fernandez

Institutions: University of Florida, Institute of Food and Agricultural Sciences

Language: English

Topic: PARP inhibition in cancer therapy

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499