The SAD1/RAD53 protein kinase controls multiple checkpoints and DNA damage-induced transcription in yeast

James B. Allen, Zheng Zhou, Wolfram Siede, Errol C. Friedberg, Stephen J. Elledge

Research output: Contribution to journalArticle

318 Citations (Scopus)

Abstract

Inhibition of DNA synthesis prevents mitotic entry through the action of the S-phase checkpoint. We have isolated S-phase arrest-defective (sad) mutants that show lethality in the presence of the DNA synthesis inhibitor hydroxyurea (HU). Several of these mutants show phenotypes consistent with inappropriate mitotic entry in the presence of unreplicated DNA, indicating a defect in the S-phase checkpoint. sad1 mutants are additionally defective for the G1 and G2 DNA damage checkpoints, and for DNA damage-induced transcription of RNR2 and RNR3. The transcriptional response to DNA damage requires activation of the Dun1 protein kinase. Activation of Dun1 in response to replication blocks or DNA damage is blocked in sad1 mutants. The HU sensitivity of sad1 mutants is suppressed by mutations in CKS1, a subunit of the p34(CDC28) kinase, further establishing a link between cell cycle progression and lethality. sad1 mutants are allelic to rad53, a radiation- sensitive mutant. SAD1 encodes an essential protein kinase. The observation that SAD1 controls three distinct checkpoints suggests a common mechanism for cell cycle arrest at these points. Together, these observations implicate protein phosphorylation in the cellular response to DNA damage and replication blocks.

Original languageEnglish (US)
Pages (from-to)2401-2415
Number of pages15
JournalGenes and Development
Volume8
Issue number20
StatePublished - Oct 15 1994

Fingerprint

Protein Kinases
DNA Damage
Yeasts
S Phase Cell Cycle Checkpoints
Hydroxyurea
Nucleic Acid Synthesis Inhibitors
DNA
Cell Cycle Checkpoints
DNA Replication
S Phase
Cell Cycle
Phosphotransferases
Phosphorylation
Radiation
Phenotype
Mutation
Proteins

Keywords

  • DNA damage
  • Protein kinase
  • protein phosphorylation
  • transcription
  • yeast

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

The SAD1/RAD53 protein kinase controls multiple checkpoints and DNA damage-induced transcription in yeast. / Allen, James B.; Zhou, Zheng; Siede, Wolfram; Friedberg, Errol C.; Elledge, Stephen J.

In: Genes and Development, Vol. 8, No. 20, 15.10.1994, p. 2401-2415.

Research output: Contribution to journalArticle

Allen, James B. ; Zhou, Zheng ; Siede, Wolfram ; Friedberg, Errol C. ; Elledge, Stephen J. / The SAD1/RAD53 protein kinase controls multiple checkpoints and DNA damage-induced transcription in yeast. In: Genes and Development. 1994 ; Vol. 8, No. 20. pp. 2401-2415.
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