One-carbon metabolic enzymes are regulated during cell division and make distinct contributions to the metabolome and cell cycle progression in Saccharomyces cerevisiae

Abstract

Enzymes of one-carbon metabolism play pivotal roles in proliferating cells. They are involved in the metabolism of amino acids, nucleotides, and lipids and the supply of all cellular methylations. However, there is limited information about how these enzymes are regulated during cell division and how cell cycle kinetics are affected in several loss-of-function mutants of one-carbon metabolism. Here, we report that the levels of the S. cerevisiae enzymes Ade17p and Cho2p, involved in the de novo synthesis of purines and phosphatidylcholine, respectively, are cell cycle-regulated. Cells lacking Ade17p, Cho2p, or Shm2p (an enzyme that supplies one-carbon units from serine) have distinct alterations in size homeostasis and cell cycle kinetics. Loss of Ade17p leads to a specific delay at START, when cells commit to a new round of cell division, while loss of Shm2p has broader effects, reducing growth rate. Furthermore, the inability to synthesize phosphatidylcholine de novo in cho2{Delta} cells delays START and reduces the coherence of nuclear elongation late in the cell cycle. Loss of Cho2p also leads to profound metabolite changes. Besides the expected changes in the lipidome, cho2{Delta} cells have reduced levels of amino acids, resembling cells shifted to poorer media. These results reveal the different ways that one-carbon metabolism allocates resources to affect cell proliferation at multiple cell cycle transitions.