A maternal requirement for glutamine synthetase I for the mitotic cycles of syncytial Drosophila embryos.
We describe the maternal effect phenotype of a hypomorphic mutation in the Drosophila gene for glutamine synthetase I (GSI). The extent of development of embryos derived from homozygous mutant females is variable, although most mutant embryos fail to survive past germband elongation and none develop into larvae. These embryos are characterised by an increase in the number of yolk-like nuclei following nuclear migration to the cortex. These nuclei appear to fall into the interior of the embryo from the cortex at blastoderm. As they do so, the majority continue to show association with PCNA in synchrony with nuclei at the cortex, suggesting some continuity of the synchrony of DNA replication. However, the occurrence of nuclei that have lost cell cycle synchrony with their neighbours is not uncommon. Immunostaining of mutant embryos revealed a range of mitotic defects, ultimately resulting in nuclear fusion events, division failure or other mitotic abnormalities. A high proportion of these mitotic figures show chromatin bridging at anaphase and telophase consistent with progression through mitosis in the presence of incompletely replicated DNA. GSI is responsible for the ATP-dependent amination of glutamate to produce glutamine, which is required in the formation of amino acids, purines and pyrimidines. We discuss how the loss of glutamine could depress both protein and DNA synthesis and lead to a variety of mitotic defects in this embryonic system that lacks certain checkpoint controls.
Frenz
L M
LM
Department of Anatomy and Physiology, University of Dundee, Scotland, UK.
Glover
D M
DM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002453:Cell Cycle; D002467:Cell Nucleus; D018076:DNA, Complementary; D004331:Drosophila melanogaster / Q000187:drug effects / Q000196:embryology / Q000201:enzymology* / Q000528:radiation effects; D015726:Giant Cells; D005974:Glutamate-Ammonia Ligase / Q000235:genetics / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D008938:Mitosis; D008969:Molecular Sequence Data; D009154:Mutation; D010087:Oxides; D010269:Paraquat; D014965:X-Rays
D018076:DNA, Complementary; D010087:Oxides; D005979:Glutathione Peroxidase; C081173:glutamine synthetase I; D005974:Glutamate-Ammonia Ligase; D010269:Paraquat