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Vol. 15, No. 20, pp. 2741-2754, October 15, 2001
1 Peter MacCallum Cancer Institute, Trescowthick Research
Laboratories, Locked Bag 1, Melbourne, Victoria 8006, Australia;
2 Division of Signal Transduction, Department of Medicine,
Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA;
3 Department of Anatomy and Cell Biology, University of
Melbourne, Parkville 3052, Australia
We have identified a Drosophila homolog of the DNA
replication initiation inhibitor Geminin (Dm geminin) and show
that it has all of the properties of Xenopus and human Geminin.
During Drosophila development, Dm Geminin is present in cycling
cells; protein accumulates during S phase and is degraded at the
metaphase to anaphase transition. Overexpression of Dm geminin
in embryos inhibits DNA replication, but cells enter mitosis arresting
in metaphase, as in dup (cdt1) mutants, and undergo
apoptosis. Overexpression of Dm Geminin also induces ectopic neural
differentiation. Dm geminin mutant embryos exhibit anaphase
defects at cycle 16 and increased numbers of S phase cells later in
embryogenesis. In a partially female-sterile Dm geminin mutant,
excessive DNA amplification in the ovarian follicle cells is observed.
Our data suggest roles for Dm Geminin in limiting DNA replication, in
anaphase and in neural differentiation.
[Key Words: Drosophila; cell cycle; DNA replication; mitosis, neurogenesis; Geminin]
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