|Sister Chromatids Fail to Separate during an Induced Endoreplication Cycle in Drosophila Embryos.|
Vidwans SJ, DiGregorio PJ, Shermoen AW, Foat B, Iwasa J, Yakubovich N, OFarrell PH
Current Biology (2002)
Category: cell division ¤ Added: May 15, 2002 ¤ Rating: ◊◊
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 . Reciprocally, persistent expression of Cyclin A/Cdk1 or Cyclin E/ Cdk2 blocks Drosophila endocycles [2, 3]. Inactivation of Cyclin A/Cdk1 by mutation or overexpression of the Cyclin/Cdk1 inhibitor, Roughex (Rux), converts the 16th embryonic mitotic cycle to an endocycle ; however, we show that Rux expression fails to convert earlier cell cycles unless Cyclin E is also downregu- lated. Following induction of a Rux transgene in Cyclin E mutant embryos during G2 of cell cycle 14 (G214), Cyclins A, B, and B3 disappeared and cells reentered S phase. This rereplication produced diplochromo- somes that segregated abnormally at a subsequent mitosis. Thus, like the yeast CKIs Rum1 and Sic1, Drosophila Rux can reset G2 cells to G1 . 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.