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

• Published in: Current biology Vol. 12; no. 10; pp. 829 - 833
• Main Authors: Vidwans, Smruti J, DiGregorio, Paul J, Shermoen, Antony W, Foat, Barrett, Iwasa, Janet, Yakubovich, Nikita, O'Farrell, Patrick H
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 14-05-2002
• Subjects: Animals; Cell Cycle; Chromatids - genetics; Chromatids - metabolism; Chromosome Segregation; Cyclin A - metabolism; Cyclin B - metabolism; Cyclin E - genetics; Cyclin E - metabolism; DNA Replication; Down-Regulation; Drosophila - cytology; Drosophila - embryology; Drosophila - genetics; Drosophila Proteins; Eye Proteins - metabolism; In Situ Hybridization, Fluorescence; Mitosis; Mutation
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/S0960-9822(02)00845-X

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, 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 [4–6]; 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 (G214), 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 [7–9]. 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.