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Fluctuations in cyclin E levels are required for multiple rounds of endocycle S phase in Drosophila.
Follette PJ, Duronio RJ, O'Farrell PH.
Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0448, USA.
The
precise cell-cycle alternation of S phase and mitosis is controlled by
alternating competence of nuclei to respond to S-phase-inducing factors
[1]. Nuclei acquire competence to replicate at the low point in
cyclin-dependent kinase (Cdk) activities that follows mitotic
destruction of cyclins. The elevation of Cdk activity late in G1 is
thought to drive cells into S phase and to block replicated DNA from
re-acquiring replication competence [2]. Whereas mitosis is normally
required to eliminate the cyclins prior to another cycle of
replication, experimental elimination of Cdk activity in G2 can restore
competence to replicate [3-6]. Here, we examine the roles of Cdks in
the endocycies of Drosophila [7]. In these cycles, rounds of discrete S
phases without intervening mitoses result in polyteny. Cyclins A and B
are lost in cells as they enter endocycles [8,9], and pulses of Cyclin
E expression drive endocycle S phases [10-12]. To address whether
oscillations of Cyclin E expression are required for endocycles, we
expressed Cyclin E continuously in Drosophila salivary glands. Growth
of the cells was severely inhibited, and a period of DNA replication
was induced but further replication was inhibited. This replication
inhibition could be overcome by the kinase inhibitor
6-dimethylaminopurine (6-DMAP), but not by expression of subunits of
the transcription factor E2F. These results indicate that endocycle S
phases require oscillations in Cdk activity, but, in contrast to
oscillations in mitotic cells, these occur independently of mitosis.
PMID: 9501987 [PubMed - indexed for MEDLINE]
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