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Vol. 14, No. 14, pp. 1765-1776, July 15, 2000
Whitehead Institute and Department of Biology, Massachusetts
Institute of Technology, Cambridge, Massachusetts 02142 USA
We identified a Drosophila gene, double parked
(dup), that is essential for DNA replication and belongs to a
new family of replication proteins conserved from
Schizosaccharomyces pombe to humans. Strong mutations in
dup cause embryonic lethality, preceded by a failure to undergo
S phase during the postblastoderm divisions. dup is required
also for DNA replication in the adult ovary, establishing that
dup is needed for DNA replication at multiple stages of
development. Strikingly, DUP protein colocalizes with the origin
recognition complex to specific sites in the ovarian follicle cells.
This suggests that DUP plays a direct role in DNA replication. The
dup transcript is cell cycle regulated and is under the control
of E2F and Cyclin E. Interestingly, dup mutant embryos fail
both to downregulate S phase genes and to engage a checkpoint
preventing mitosis until completion of S phase. This could be either
because these events depend on progression of S phase beyond the point
blocked in the dup mutants or because DUP is needed directly
for these feedback mechanisms.
[Key Words: DNA replication; amplification; cell cycle; Cdt1; E2F]
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