PMID:16648644

Citation	Ciapponi, L, Cenci, G and Gatti, M (2006) The Drosophila Nbs protein functions in multiple pathways for the maintenance of genome stability. Genetics 173:1447-54
Abstract	The Mre11/Rad50/Nbs (MRN) complex and the two protein kinases ATM and ATR play critical roles in the response to DNA damage and telomere maintenance in mammalian systems. It has been previously shown that mutations in the Drosophila mre11 and rad50 genes cause both telomere fusion and chromosome breakage. Here, we have analyzed the role of the Drosophila nbs gene in telomere protection and the maintenance of chromosome integrity. Larval brain cells of nbs mutants display telomeric associations (TAs) but the frequency of these TAs is lower than in either mre11 or rad50 mutants. Consistently, Rad50 accumulates in the nuclei of wild-type cells but not in those of nbs cells, indicating that Nbs mediates transport of the Mre11/Rad50 complex in the nucleus. Moreover, epistasis analysis revealed that rad50 nbs, tefu (ATM) nbs, and mei-41 (ATR) nbs double mutants have significantly higher frequencies of TAs than either of the corresponding single mutants. This suggests that Nbs and the Mre11/Rad50 complex play partially independent roles in telomere protection and that Nbs functions in both ATR- and ATM-controlled telomere protection pathways. In contrast, analysis of chromosome breakage indicated that the three components of the MRN complex function in a single pathway for the repair of the DNA damage leading to chromosome aberrations.
Links	PubMed PMC1526684 Online version:10.1534/genetics.106.058081
Keywords	Animals; Apoptosis/genetics; Carrier Proteins/genetics; Carrier Proteins/physiology; Cell Cycle Proteins/genetics; Cell Cycle Proteins/metabolism; Chromosomal Proteins, Non-Histone/genetics; Chromosomal Proteins, Non-Histone/metabolism; Chromosome Breakage; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila Proteins/physiology; Drosophila melanogaster/genetics; Drosophila melanogaster/metabolism; Endodeoxyribonucleases/genetics; Endodeoxyribonucleases/metabolism; Exodeoxyribonucleases/genetics; Exodeoxyribonucleases/metabolism; Genomic Instability; Interphase; Larva/cytology; Larva/metabolism; Microscopy, Fluorescence; Models, Biological; Mutation; Protein-Serine-Threonine Kinases/genetics; Protein-Serine-Threonine Kinases/metabolism; Protein-Serine-Threonine Kinases/physiology; Signal Transduction/genetics; Signal Transduction/physiology; Telomere/genetics; Telomere/physiology
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