TEL1, an S. cerevisiae homolog of the human gene mutated in ataxia telangiectasia, is functionally related to the yeast checkpoint gene MEC1.
Patients with the genetic disorder ataxia telangiectasia (AT) have mutations in the AT mutated (ATM) gene, which is homologous to TEL1 and the checkpoint gene MEC1. A tel1 deletion mutant, unlike a mec1 deletion, is viable and does not exhibit increased sensitivity to DNA-damaging agents. However, increased dosage of TEL1 rescues sensitivity of a mec1 mutant, mec1-1, to DNA-damaging agents and rescues viability of a mec1 disruption. mec1-1 tel1 delta 1 double mutants are synergistically sensitive to DNA-damaging agents, including radiomimetic drugs. These data indicate that TEL1 and MEC1 are functionally related and that functions of the ATM gene are apparently divided between at least two S. cerevisiae homologs.
Morrow
D M
DM
Department of Molecular Biology and Genetics, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.
Tagle
D A
DA
Shiloh
Y
Y
Collins
F S
FS
Hieter
P
P
D001260:Ataxia Telangiectasia / Q000235:genetics*; D001483:Base Sequence; D001761:Bleomycin / Q000494:pharmacology; D003001:Cloning, Molecular; D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects; D005656:Fungal Proteins / Q000235:genetics*; D005720:Gamma Rays; D005800:Genes, Fungal / Q000502:physiology*; D006801:Humans; D006918:Hydroxyurea; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics / Q000528:radiation effects; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D013308:Streptonigrin / Q000494:pharmacology; D014466:Ultraviolet Rays
D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D029701:Saccharomyces cerevisiae Proteins; D001761:Bleomycin; D013308:Streptonigrin; D017346:Protein Serine-Threonine Kinases; C513623:TEL1 protein, S cerevisiae; D006918:Hydroxyurea