Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Inactivation of Ku-mediated end joining suppresses mec1Delta lethality by depleting the ribonucleotide reductase inhibitor Sml1 through a pathway controlled by Tel1 kinase and the Mre11 complex.

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 mec1Delta, but not rad53Delta, lethality. We show that suppression of mec1Delta 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, mec1Delta lethality is also suppressed by lif1Delta, which like yku70Delta and yku80Delta, prevents nonhomologous end joining. The viability of yku70Delta mec1Delta and yku80Delta mec1Delta 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.

Pubmed ID: 16287875


  • Corda Y
  • Lee SE
  • Guillot S
  • Walther A
  • Sollier J
  • Arbel-Eden A
  • Haber JE
  • Géli V


Molecular and cellular biology

Publication Data

December 18, 2005

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM61766

Mesh Terms

  • Cell Cycle
  • Cell Cycle Proteins
  • Cell Death
  • Checkpoint Kinase 2
  • DNA-Binding Proteins
  • Endodeoxyribonucleases
  • Exodeoxyribonucleases
  • Fungal Proteins
  • Gene Expression Regulation, Fungal
  • Genes, Lethal
  • Intracellular Signaling Peptides and Proteins
  • Protein Binding
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • RNA, Messenger
  • Ribonucleotide Reductases
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Signal Transduction