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Sister Chromatids Fail to Separate during an Induced Endoreplication Cycle in Drosophila Embryos Export

Current Biology, Vol. 12, No. 10. (14 May 2002), pp. 829-833.

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endoreplication

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When mitosis is bypassed, as in some cancer cells or in natural endocycles, sister chromosomes remain paired and produce four-stranded diplochromosomes or polytene chromosomes. Cyclin/Cdk1 inactivation blocks entry into mitosis and can reset G2 cells to G1, allowing another round of replication [1] . Reciprocally, persistent expression of Cyclin A/Cdk1 or Cyclin E/Cdk2 blocks Drosophila endocycles [2] and [3] . Inactivation of Cyclin A/Cdk1 by mutation or overexpression of the Cyclin/Cdk1 inhibitor, Roughex (Rux), converts the 16 th embryonic mitotic cycle to an endocycle [4] , [5] and [6] ; however, we show that Rux expression fails to convert earlier cell cycles unless Cyclin E is also downregulated. Following induction of a Rux transgene in Cyclin E mutant embryos during G2 of cell cycle 14 (G2 14 ), Cyclins A, B, and B3 disappeared and cells reentered S phase. This rereplication produced diplochromosomes that segregated abnormally at a subsequent mitosis. Thus, like the yeast CKIs Rum1 and Sic1, Drosophila Rux can reset G2 cells to G1 [7] , [8] and [9] . The observed cyclin destruction suggests that cell cycle resetting by Rux was associated with activation of the anaphase-promoting complex (APC), while the presence of diplochromosomes implies that this activation of APC outside of mitosis was not sufficient to trigger sister disjunction.


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