Genes controlling essential cell-cycle functions in Drosophila melanogaster.

Abstract

On the basis of the hypothesis that mutants in genes controlling essential cell cycle functions in Drosophila should survive up to the larval-pupal transition, 59 such 'late lethals' were screened for those mutants affecting cell division. Examination of mitosis in brain neuroblasts revealed that 30 of these lethals cause disruptions in mitotic chromosome behavior. These mutants identify genes whose wild-type functions are important for: (1) progression through different steps of interphase, (2) the maintenance of mitotic chromosome integrity, (3) chromosome condensation, (4) spindle formation and/or function, and (5) completion of cytokinesis or completion of chromosome segregation. The presence of mitotic defects in late lethal mutants is correlated tightly with the presence of defective imaginal discs. Thus, the phenotypes of late lethality and poorly developed imaginal discs are together almost diagnostic of mutations in essential cell-cycle functions. The terminal phenotypes exhibited by these Drosophila mitotic mutants are remarkably similar to those observed in mammalian cell-cycle mutants, suggesting that these diverse organisms use a common genetic logic to regulate and integrate the events of the cell cycle.

The three postblastoderm cell cycles of Drosophila embryogenesis are regulated in G2 by string

“…By inducing stg ectopically at different times during embryogenesis, we find that stg mRNA can induce mitosis in virtually all of the embryonic cells during the G2 periods of cell cycles 14, 15, and 16. This demonstrates that other factors required for mitosis are present at functionally sufficient levels throughout the embryo during these cycles (e.g., cyclins, cdc2, and other factors; see O'Farrell, 1989, 1990; C. F. Lehner and P. H. O., submitted;Gatti and Baker, 1989). Since stg mRNA expression normally occurs in each cell at the end of G2, just prior to each of these mitoses, we believe that stg mRNA levels do indeed cause the mitotic pattern seen during these cycles.…”

A human homolog of Drosophila lethal(3)malignant brain tumor (l(3)mbt) protein associates with condensed mitotic chromosomes

“…CCF (centrosomal and chromosomal factor), which shares homology to the chromatin-binding sites of the Psc protein, is required for the proper condensation of mitotic chromosomes (Kodjabachian et al, 1998). Enhancer of zeste, which was identi®ed as a component of di erent PcG-like chromatin-binding complex, is required to maintain chromosome integrity during mitosis (Gatti et al, 1989;Jones et al, 1998;Sewalt et al, 1998;van Lohuizen et al, 1998). These ®ndings allow us to speculate that h-l(3)mbt, which shares homology with the functional domains of some PcG proteins, may take part in the proper condensation of mitotic chromosomes.…”

Delays in anaphase initiation occur in individual nuclei of the syncytial Drosophila embryo.

“…This analysis is based on previous studies of Drosophila neuroblast cell division errors (Gatti et al, 1974;Ripoll et al, 1985;Gatti and Baker, 1989;Gatti and Goldberg, 1991). Division errors that produce chromosome aberrations can be detected by screening for chromosome fragments.…”