A SUPPRESSOR OF 2 ESSENTIAL CHECKPOINT GENES IDENTIFIES A NOVEL PROTEIN THAT NEGATIVELY AFFECTS DNTP POOLS

In Saccharomyces cerevisiae, MEC1 and RAD53 are essential for cell gro wth and checkpoint function. Their essential role in growth can be byp assed by deletion of a novel gene, SML1, which functions after several genes whose overexpression also suppresses mec1 inviability. In addit ion, smI1 affects various cellular processes analogous to overproducin g the large subunit of ribonucleotide reductase, RMR1. These include e ffects on mitochondrial biogenesis, on the DNA damage response, and on cell growth. Consistent with these observations, the levels of dNTP p ools in sm/1 Delta strains are increased compared to wild-type. This e ffect is not due to an increase in RNR transcription. Finally, both in vivo and in vitro experiments show that SmI1 binds to Rnr1. We propos e that SmI1 inhibits dNTP synthesis posttranslationally by binding dir ectly to Rnr1 and that Mec1 and Rad53 are required to relieve this inh ibition.