Mutations in nucleotide metabolism genes bypass proteasome defects in png-1/NGLY1-deficient Caenorhabditis elegans

Regulation of the proteasome is disrupted in the rare genetic disease known as NGLY1 deficiency. This manuscript finds that proteasome dysfunction in NGLY1-deficient C. elegans depends on nucleotide availability, indicating an unexpected regulatory crosstalk between nucleotide metabolism and protein turnover, and suggesting that interventions to alter nucleotide availability might mitigate proteasome insufficiency in diseases associated with proteasome dysfunction.