The Pof1 nicotinamide mononucleotide adenylyl transferase has a non-canonical role in NAD+ metabolism in the budding yeast Saccharomyces cerevisiae

synthesis domain of Pof1 may affect ATPase activity or NMN binding. Moreover, an inverse correlation between the expression of NMNATs and nucleotidases under nutritional stress also contributes to pof1Δ-associated NR production. Supporting this, NR production is enhanced upon moderate glucose depletion, while Pof1 protein is reduced. Overall, our data suggest that in pof1Δ cells, NMN is likely more accessible to the nucleotidases, resulting in NR production. Additionally, the similarity between NR production and nucleotide degradation indicates that NR production is likely important under replication stress. We show that NR levels positively correlate with resistance to replication stress. Our findings help understand the critical role of Pof1 in modulating NR production and the putative role of NR in overall nucleotide metabolism.