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E type cyclins (E1 and E2) are believed to drive cell entry into the S phase. It is widely assumed that the two E type cyclins are critically required for proliferation of all cell types. Here, we demonstrate that E type cyclins are largely dispensable for mouse development. However, endoreplication of trophoblast giant cells and megakaryocytes is severely impaired in the absence of cyclin E. Cyclin E-deficient cells proliferate actively under conditions of continuous cell cycling but are unable to reenter the cell cycle from the quiescent G(0) state. Molecular analyses revealed that cells lacking cyclin E fail to normally incorporate MCM proteins into DNA replication origins during G(0)-->S progression. We also found that cyclin E-deficient cells are relatively resistant to oncogenic transformation. These findings define a molecular function for E type cyclins in cell cycle reentry and reveal a differential requirement for cyclin E in normal versus oncogenic proliferation.

Type

Journal article

Journal

Cell

Publication Date

22/08/2003

Volume

114

Pages

431 - 443

Keywords

Animals, Cardiovascular Abnormalities, Cell Cycle, Cell Transformation, Neoplastic, Cyclin E, DNA Replication, Embryo, Mammalian, Female, Gene Targeting, Male, Megakaryocytes, Mice, Mice, Knockout, Placenta, Pregnancy, Spermatogenesis, Trophoblasts