Kinase-independent function of cyclin E

Mol Cell. 2007 Jan 12;25(1):127-39. doi: 10.1016/j.molcel.2006.11.029.


E-type cyclins are thought to drive cell-cycle progression by activating cyclin-dependent kinases, primarily CDK2. We previously found that cyclin E-null cells failed to incorporate MCM helicase into DNA prereplication complex during G(0) --> S phase progression. We now report that a kinase-deficient cyclin E mutant can partially restore MCM loading and S phase entry in cyclin E-null cells. We found that cyclin E is loaded onto chromatin during G(0) --> S progression. In the absence of cyclin E, CDT1 is normally loaded onto chromatin, whereas MCM is not, indicating that cyclin E acts between CDT1 and MCM loading. We observed a physical association of cyclin E with CDT1 and with MCMs. We propose that cyclin E facilitates MCM loading in a kinase-independent fashion, through physical interaction with CDT1 and MCM. Our work indicates that-in addition to their function as CDK activators-E cyclins play kinase-independent functions in cell-cycle progression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / metabolism
  • Chromatin / metabolism
  • Cyclin E / deficiency
  • Cyclin E / metabolism*
  • Cyclin-Dependent Kinases / metabolism*
  • DNA Helicases / metabolism
  • DNA-Binding Proteins / metabolism
  • HeLa Cells
  • Humans
  • Mice
  • Models, Biological
  • Mutant Proteins / metabolism
  • Oncogenes
  • Phenotype
  • Protein Binding
  • Protein Transport
  • Resting Phase, Cell Cycle
  • S Phase


  • Cell Cycle Proteins
  • Chromatin
  • Cyclin E
  • DNA-Binding Proteins
  • Mutant Proteins
  • Ris2 protein, mouse
  • Cyclin-Dependent Kinases
  • DNA Helicases