Unprotected Drosophila melanogaster telomeres activate the spindle assembly checkpoint

• Published in: Nature genetics Vol. 40; no. 3; pp. 362 - 366
• Main Authors: Musarò, Mariarosaria, Ciapponi, Laura, Fasulo, Barbara, Gatti, Maurizio, Cenci, Giovanni
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.03.2008; Nature Publishing Group
• Subjects: Agriculture; Animal Genetics and Genomics; Animals; Animals, Genetically Modified; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cdc20 Proteins; Cell cycle; Cell Cycle - genetics; Cell Cycle - physiology; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Checkpoint Kinase 1; Chromosomal Proteins, Non-Histone - genetics; Chromosomal Proteins, Non-Histone - metabolism; Cytoskeletal Proteins - metabolism; Deoxyribonucleic acid; DNA; DNA damage; DNA Damage - genetics; DNA Damage - physiology; Drosophila melanogaster; Drosophila melanogaster - genetics; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Endodeoxyribonucleases - genetics; Exodeoxyribonucleases - genetics; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Function; Gene mutations; Genes, cdc; Genetic aspects; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Human Genetics; Insects; letter; Mammals; Microtubule-Associated Proteins - genetics; Models, Biological; Mutants; Mutation; Physiological aspects; Protein Binding; Protein Kinases - genetics; Protein Serine-Threonine Kinases - genetics; Proteins; Spindle Apparatus - genetics; Spindle Apparatus - metabolism; Spindle Apparatus - physiology; Telomere - metabolism; Telomere - physiology; Telomeres; Yeasts; Italy; Arthropoda; Insecta; Invertebrata; Drosophila melanogaster; Telomere; Diptera; Drosophilidae
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.2007.64

In both yeast and mammals, uncapped telomeres activate the DNA damage response (DDR) and undergo end-to-end fusion 1 , 2 . Previous work has shown that the Drosophila HOAP protein, encoded by the caravaggio ( cav ) gene, is required to prevent telomeric fusions 3 . Here we show that HOAP-depleted telomeres activate both the DDR and the spindle assembly checkpoint (SAC). The cell cycle arrest elicited by the DDR was alleviated by mutations in mei-41 (encoding ATR), mus304 (ATRIP), grp (Chk1) and rad50 but not by mutations in tefu (ATM). The SAC was partially overridden by mutations in zw10 (also known as mit(1)15 ) and bubR1 , and also by mutations in mei-41 , mus304 , rad50 , grp and tefu . As expected from SAC activation, the SAC proteins Zw10, Zwilch, BubR1 and Cenp-meta (Cenp-E) accumulated at the kinetochores of cav mutant cells. Notably, BubR1 also accumulated at cav mutant telomeres in a mei-41 -, mus304 -, rad50 -, grp - and tefu -dependent manner. Our results collectively suggest that recruitment of BubR1 by dysfunctional telomeres inhibits Cdc20-APC function, preventing the metaphase-to-anaphase transition.