Sister chromatids fail to separate during an induced endoreplication cycle in Drosophila embryos.
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. 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; 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. 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.
Vidwans
Smruti J
SJ
Department of Biochemistry and Biophysics, University of California, San Francisco, Box 0448, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
DiGregorio
Paul J
PJ
Shermoen
Antony W
AW
Foat
Barrett
B
Iwasa
Janet
J
Yakubovich
Nikita
N
O'Farrell
Patrick H
PH
D000818:Animals; D002453:Cell Cycle; D002842:Chromatids / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation; D019925:Cyclin A / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication; D015536:Down-Regulation; D004330:Drosophila / Q000166:cytology* / Q000196:embryology* / Q000235:genetics; D029721:Drosophila Proteins; D005136:Eye Proteins / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D008938:Mitosis; D009154:Mutation
C503698:CycB protein, Drosophila; D019925:Cyclin A; D019926:Cyclin B; D019927:Cyclin E; D029721:Drosophila Proteins; D005136:Eye Proteins; C088084:rux protein, Drosophila