MEC1 and RAD53 are two essential genes that are also
involved in DNA checkpoint functions in S. cerevisiae . Homologs
of Mec1 in human and mice, ATM and Atm, respectively, play similar dual
roles. Mutations in ATM result in ataxia telangiectasia (AT), a
cancer-prone disease. Given the conservation between these proteins,
investigating the mitotic growth function of Mec1 in yeast may shed
light on the functions of ATM and Atm. Here, we report the
identification and characterization of a mutation, sml1 , that
permits cell growth in the absence of Mec1 and Rad53. The SML1
gene encodes a novel protein with no known homologs in yeast or any
other organism. Suppression of mec1 lethality by sml1 does
not require the function of Rad53, Dun1 or Tel1. We found that
sml1 strains are more resistant to DNA damaging agents. In
addition, deletion of the SML1 gene suppresses the sensitivity of
dun1 mutants to DNA damage. The deletion also affects
mitochondrial biogenesis in an analogous manner to overexpressing the
large subunit of ribonucleotide reductase (Rnr1). Co-immunoprecipitation
experiments show that Sml1 binds to Rnr1 in vivo . Furthermore,
direct measurement of the dNTP pools reveals an increase in sml1
strains. Based on these results, we propose that Sml1 inhibits dNTP
synthesis post-transcriptionally by binding directly to Rnr1 and that
Mec1 and Rad53 are required to relieve this inhibition at S phase.
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