Quartet: A Drosophila developmental mutation affecting chromosome separation in mitosis

Abstract

The Drosophila mutation, quartet, affects development at points in the life cycle that require intense mitotic activity. Examination of embryos affected by the maternal effect of quartet has revealed defects that can be attributed to incomplete chromosome separation at mitosis. These defects include uneven spacing of nuclei, strands of DNA creating bridges between nuclei, and abnormal amounts of DNA per nucleus. Nuclei in quartet-affected embryos also have a greater-than-normal number of centrosomes. Immunofluorescent examination of the spindles in quartet-affected embryos has revealed tripolar spindles and adjacent spindles that share a common spindle pole. Finally, chromosome separation distance was measured in anaphase and telophase spindles in quartet-affected embryos and found to be blocked in anaphase. Examination of mitotic figures in quartet larvae revealed a reduced mitotic index and an elevated frequency of abnormal mitotic figures. quartet could encode a function necessary for the disengagement of chromosomes in mitosis, for kinetochore function or for function of a spindle motor. Mutations in quartet prevent the post-translational modification of three abundant proteins. These proteins may be involved in chromosome separation in mitosis.

Chromosome tangling and breakage at anaphase result from mutations in lodestar, a Drosophila gene encoding a putative nucleoside triphosphate-binding protein.

“…These "extra" centrosomes would appear to have become dissociated from their nuclei, and we assume that they are undergoing cycles of division. The uncoupling of centrosome replication from nuclear replication during the Drosophila syncytial cycles has been demonstrated previously by using the DNA polymerase inhibitor aphidicolin (Raft andGlover 1988, 1989) and has been observed in other mitotic mutants such as giant nuclei (Freeman et al 1986), abnormal spindle ), abnormal chromatin (Vessey et al 1991}, and quartet (Zahner and Cheney 1990).…”

Interaction of Sec4 with GDI proteins from bovine brain, Drosophila melanogaster and Saccharomyces cerevisiae

“…dGD1 is the third rab GDI protein to be identified and was isolated by its association with the Drosophila developmental mutation quartet [33]. Quartet causes late larval lethality, small imaginal discs and low mitotic activity in larval brains and a basic shift in the isoelectric point of three abundant proteins [38,39,40]. One of these proteins was purified and an antibody raised that allowed cloning and sequencing of the cDNA.…”

A Drosophila homolog of bovine smg p25a GDP dissociation inhibitor undergoes a shift in isoelectric point in the developmental mutant quartet.

“…A reduced mitotic index with an elevated frequency of abnormal mitotic figures has been seen in the larval brains of four quartet alleles (31,47). In the abnormal mitotic figures, common abnormalities seen are fragmented chromosomes and incompletely condensed chromosomes.…”

“…Developmental defects in quartet animals involve late larval lethality, small imaginal discs, and reduced mitotic activity in larval brains (31,32,47). When expressed in the adult female, quartet mutations produce a maternal lethal effect on the embryo, with incomplete chromosome separation during early embryonic mitotic divisions (47).…”