The role of copper/zinc-containing superoxide dismutase (cSOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) in metabolic defense against 02 toxicity in Drosophila is examined through the properties of a mutant strain carrying a cSOD-null mutation, cSOD1'08. Homozygotes are viable as larvae, which indicates that cSOD is not essential for cell viability per se. cSOD"'0 confers recessive sensitivity to the superoxide anion (O )-generator paraquat and to the transition metal compound CuS04, which indicates that the cSOD-nufl condition in fact leads to impaired°2 metabolism.The primary biological consequences of the reduced°2 dismutation capacity of cSOD"IY Drosophila are realized in the adult as infertility and reduction in life-span. We conclude that the infertility and reduced life-span of cSODR"'O adults arise as a consequence of the reduced capacity of embryos, larvae, and pupae to adequately protect developing preimaginal cells from 02-jnitiated cytotoxic damage.
We propose that the primary defect in grp-derived embryos is a failure to replicate or repair DNA completely before mitotic entry during the late syncytial divisions. This suggests that wild-type grp functions in a developmentally regulated DNA replication/damage checkpoint operating during the late syncytial divisions. These results are discussed with respect to the proposed function of the chk1/rad27 gene.
The scalloped {sd) gene of Drosophila melanogaster was initially characterized by mutants affecting structures on the wing of the adult fly. The sequence of a cDNA clone of the gene reveals a predicted protein sequence homologous to that of a human transcriptional enhancer factor, TEF-1 (68% identity). The homology includes a sequence motif, the TEA domain, that was shown previously to be a DNA-binding domain of TEF-1. An sd enhancer trap strain expresses the reporter gene in a subset of neuroblasts in the central nervous system and in the peripheral sense organs of the embryo. The reporter gene is later expressed in specific regions of the imaginal discs, including regions of the wing disc destined to become structures defective in viable sd mutants. Later still, expression in the adult brain is restricted to subsets of cells, some in regions involved in the processing of gustatory information. These observations indicate that the sd gene encodes a transcription factor that functions in the regulation of cell-specific gene expression during Drosophila development, particularly in the differentiation of the nervous system.
The cyclin proteolysis that accompanies the exit from mitosis in diverse systems appears to be essential for restoration of interphase. The early syncytial divisions of Drosophila embryos, however, occur without detectable oscillations in the total cyclin level or Cdk1 activity. Nonetheless, we found that injection of an established inhibitor of cyclin proteolysis, a cyclin B amino-terminal peptide, prevents exit from mitosis in syncytial embryos. Similarly, injection of a version of Drosophila cyclin B that is refractory to proteolysis results in mitotic arrest. We infer that proteolysis of cyclins is required for exit from syncytial mitoses. This inference can be reconciled with the failure to observe oscillations in total cyclin levels if only a small pool of cyclins is destroyed in each cycle. We find that antibody detection of histone H3 phosphorylation (PH3) acts as a reporter for Cdk1 activity. A gradient of PH3 along anaphase chromosomes suggests local Cdk1 inactivation near the spindle poles in syncytial embryos. This pattern of Cdk1 inactivation would be consistent with local cyclin destruction at centrosomes or kinetochores. The local loss of PH3 during anaphase is specific to the syncytial divisions and is not observed after cellularization. We suggest that exit from mitosis in syncytial cycles is modified to allow nuclear autonomy within a common cytoplasm.
ATM and ATR display distinct activities in meiotic DSB repair, such that ATM functions in DNA damage repair and negative feedback control over programmed double strand breaks, whereas ATR is required for checkpoint activity.
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