ATM is required for telomere maintenance and chromosome stability during Drosophila development.
ATM is a large, multifunctional protein kinase that regulates responses required for surviving DNA damage: including DNA repair, apoptosis, and cell cycle checkpoints. Here, we show that Drosophila ATM function is essential for normal adult development. Extensive, inappropriate apoptosis occurs in proliferating atm mutant tissues, and in clonally derived atm mutant embryos, frequent mitotic defects were seen. At a cellular level, spontaneous telomere fusions and other chromosomal abnormalities are common in atm larval neuroblasts, suggesting a conserved and essential role for dATM in the maintenance of normal telomeres and chromosome stability. Evidence from other systems supports the idea that DNA double-strand break (DSB) repair functions of ATM kinases promote telomere maintenance by inhibition of illegitimate recombination or fusion events between the legitimate ends of chromosomes and spontaneous DSBs. Drosophila will be an excellent model system for investigating how these ATM-dependent chromosome structural maintenance functions are deployed during development. Because neurons appear to be particularly sensitive to loss of ATM in both flies and humans, this system should be particularly useful for identifying cell-specific factors that influence sensitivity to loss of dATM and are relevant for understanding the human disease, ataxia-telangiectasia.
Department of Biological Sciences, University of Alberta, Edmonton, Alberta, T6G 2E9, Canada.
Elizabeth
E
Silva
Stanley
S
Tiong
Michael
M
Pedersen
Ellen
E
Homola
Anne
A
Royou
Barbara
B
Fasulo
Giorgia
G
Siriaco
Shelagh D
SD
Campbell
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D064007:Ataxia Telangiectasia Mutated Proteins; D019521:Body Patterning / Q000502:physiology*; D018797:Cell Cycle Proteins; D043171:Chromosomal Instability / Q000502:physiology*; D003433:Crosses, Genetic; D004260:DNA Repair; D004268:DNA-Binding Proteins; D004330:Drosophila / Q000254:growth & development* / Q000648:ultrastructure; D005123:Eye / Q000473:pathology; D007814:Larva / Q000254:growth & development / Q000648:ultrastructure; D008124:Locomotion / Q000502:physiology; D008854:Microscopy, Electron; D016296:Mutagenesis; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011995:Recombination, Genetic / Q000502:physiology; D016615:Telomere / Q000502:physiology*; D013696:Temperature; D019076:Transgenes / Q000235:genetics; D025521:Tumor Suppressor Proteins; D014921:Wings, Animal / Q000473:pathology
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases