High impact information on SHM1

• Influence of the nuclear gene tmp3 on the loss of mitochondrial genes in Saccharomyces cerevisiae [1].
• The tmp3 mutant quickly loses its mitochondrial genome even when grown on fully supplemented medium or on a high concentration of 5-formyl tetrahydrofolate, which replaces all the four requirements [1].
• The Saccharomyces cerevisiae tmp3 mutant is deficient in the mitochondrial enzyme complex that participates in the formation of one-carbon-group-tetrahydrofolate coenzymes, serine transhydroxymethylase, dihydrofolate reductase, and thymidylate synthetase, thus leading to multiple nutritional requirements of dTMP, adenine, histidine, and methionine [1].
• The SHM2 gene but not the SHM1 gene has putative GCN4 sites upstream of the putative TATA box, suggesting regulation of its transcription by the general amino acid control system [2].
• Mutagenesis of the double-disrupted, shm1 shm2 yeast yielded strains of a single complementation group that are auxotrophic for glycine [2].

Biological context of SHM1

• The genes encoding both the cytosolic and mitochondrial serine hydroxymethyltransferases (SHM2 and SHM1, respectively) and a third unidentified gene of the yeast Saccharomyces cerevisiae have been isolated and their nucleotide sequences determined [2].
• Lethality in the absence of the mitochondrial Shm1 and the cytoplasmic Ade3 enzymes indicates that, under certain circumstances, these cellular compartments cooperate in carrying out essential metabolic processes [3].
• In vitro studies have considered the kinetics of the C1-THF synthase/SHMT enzyme system in the catalytic conversion of formate to serine [Strong et al. (1987) J. Biol. Chem. 262, 12519-12525] [4].

Anatomical context of SHM1

• Inactivation of SHM1, SHM2 and ADE3 is required to render yeast auxotrophic for TMP and methionine, suggesting that TMP synthesized in mitochondria may be available to the cytoplasmic compartment [5].

Associations of SHM1 with chemical compounds

• Gene disruption studies demonstrated that inactivation of SHM1, SHM2, and GLY1 is required to yield yeast that are completely auxotrophic for glycine [2].
• With the inactivation of SHM1, however, the glycine cleavage system can make an observable contribution to the level of mitochondrial formate [5].
• Genes encoding the mitochondrial (SHM1) and cytosolic (SHM2) serine hydroxymethyltransferases, and the L-threonine aldolase gene (GLY1) from Candida albicans were cloned and sequenced [6].
• Growth experiments using glucose as the sole carbon source showed that GLY1 is more important for glycine biosynthesis than SHM1 and SHM2 encoding alternative serine hydroxymethyltransferases [7].
• However, when both serine and glycine were present, the mitochondrial SHMT made a significant contribution of one-carbon units, but not glycine, for purine synthesis [8].

Other interactions of SHM1

• We report that mutations in the HIP1 and SHM1 genes exhibit synthetic lethality with ade3 deletions [3].
• Growth of shm1 shm2 mutants was stimulated by glycine, whereas glycine could not supplement the growth of the isogenic gcv1 strain [9].

References