Molecular Cell
Volume 25, Issue 1, 12 January 2007, Pages 127-139
Journal home page for Molecular Cell

Article
Kinase-Independent Function of Cyclin E

https://doi.org/10.1016/j.molcel.2006.11.029Get rights and content
Under an Elsevier user license
open archive

Summary

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 G0 → 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 G0 → 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.

SIGNALING
CELLCYCLE

Cited by (0)

8

These authors contributed equally to this work.