Unprotected Drosophila melanogaster telomeres activate the spindle assembly checkpoint.
In both yeast and mammals, uncapped telomeres activate the DNA damage response (DDR) and undergo end-to-end fusion. Previous work has shown that the Drosophila HOAP protein, encoded by the caravaggio (cav) gene, is required to prevent telomeric fusions. 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.
Musarò
Mariarosaria
M
Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali (DiSTeBA), Università del Salento, Lecce 73100, Italy.
Ciapponi
Laura
L
Fasulo
Barbara
B
Gatti
Maurizio
M
Cenci
Giovanni
G
D000818:Animals; D030801:Animals, Genetically Modified; D064199:Cdc20 Proteins; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D000071877:Checkpoint Kinase 1; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004249:DNA Damage / Q000235:genetics / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics*; D004706:Endodeoxyribonucleases / Q000235:genetics; D005090:Exodeoxyribonucleases / Q000235:genetics; D018816:Genes, cdc; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008954:Models, Biological; D011485:Protein Binding; D011494:Protein Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016615:Telomere / Q000378:metabolism* / Q000502:physiology*
C118001:APC protein, Drosophila; C506005:BubR1 protein, Drosophila; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D008869:Microtubule-Associated Proteins; C474841:Zwilch protein, Drosophila; C471206:cav protein, Drosophila; C411730:cmet protein, Drosophila; C577502:fzy protein, Drosophila; C076055:Zw10 protein, Drosophila; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1; C444435:Mei-41 protein, Drosophila; D017346:Protein Serine-Threonine Kinases; C514947:Tefu protein, Drosophila; C000605877:grp protein, Drosophila; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; C492905:Rad50 protein, Drosophila