Phosphorylation of Sld2 and Sld3 by cyclin-dependent kinases promotes DNA replication in budding yeast

Nature. 2007 Jan 18;445(7125):281-5. doi: 10.1038/nature05432. Epub 2006 Dec 13.


Cyclin-dependent kinases (CDKs) drive major cell cycle events including the initiation of chromosomal DNA replication. We identified two S phase CDK (S-CDK) phosphorylation sites in the budding yeast Sld3 protein that, together, are essential for DNA replication. Here we show that, when phosphorylated, these sites bind to the amino-terminal BRCT repeats of Dpb11. An Sld3-Dpb11 fusion construct bypasses the requirement for both Sld3 phosphorylation and the N-terminal BRCT repeats of Dpb11. Co-expression of this fusion with a phospho-mimicking mutant in a second essential CDK substrate, Sld2, promotes DNA replication in the absence of S-CDK. Therefore, Sld2 and Sld3 are the minimal set of S-CDK targets required for DNA replication. DNA replication in cells lacking G1 phase CDK (G1-CDK) required expression of the Cdc7 kinase regulatory subunit, Dbf4, as well as Sld2 and Sld3 bypass. Our results help to explain how G1- and S-CDKs promote DNA replication in yeast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / metabolism*
  • Cyclin-Dependent Kinases / metabolism*
  • DNA Replication*
  • DNA, Fungal / biosynthesis
  • DNA-Binding Proteins / metabolism*
  • G1 Phase
  • Phosphorylation
  • Protein Binding
  • S Phase
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Saccharomycetales / cytology
  • Saccharomycetales / enzymology
  • Saccharomycetales / genetics
  • Saccharomycetales / metabolism*
  • Surface Plasmon Resonance


  • Cell Cycle Proteins
  • DNA, Fungal
  • DNA-Binding Proteins
  • DPB11 protein, S cerevisiae
  • SLD2 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Sld3 protein, S cerevisiae
  • Cyclin-Dependent Kinases