Abstract
RAD53
and
MEC1
are essential
Saccharomyces cerevisiae
genes required for the DNA replication and DNA damage checkpoint responses. Their lethality can be suppressed by increasing the intracellular pool of deoxynucleotide triphosphates. We report that deletion of
YKU70
or
YKU80
suppresses
mec1
Δ, but not
rad53
Δ, lethality. We show that suppression of
mec1
Δ lethality is not due to Ku
−
-associated telomeric defects but rather results from the inability of Ku
−
cells to efficiently repair DNA double strand breaks by nonhomologous end joining. Consistent with these results,
mec1
Δ lethality is also suppressed by
lif1
Δ, which like
yku70
Δ and
yku80
Δ, prevents nonhomologous end joining. The viability of
yku70
Δ
mec1
Δ and
yku80
Δ
mec1
Δ cells depends on the ATM-related Tel1 kinase, the Mre11-Rad50-Xrs2 complex, and the DNA damage checkpoint protein Rad9. We further report that this Mec1-independent pathway converges with the Rad53/Dun1-regulated checkpoint kinase cascade and leads to the degradation of the ribonucleotide reductase inhibitor Sml1.