Letter abstract
Nature Genetics 40, 362 - 366 (2008)
Published online: 3 February 2008 | doi:10.1038/ng.2007.64
Unprotected Drosophila melanogaster telomeres activate the spindle assembly checkpoint
Mariarosaria Musarò1,2, Laura Ciapponi2, Barbara Fasulo3, Maurizio Gatti2 & Giovanni Cenci1,4
In both yeast and mammals, uncapped telomeres activate the DNA damage response (DDR) and undergo end-to-end fusion1, 2. Previous work has shown that the Drosophila HOAP protein, encoded by the caravaggio (cav) gene, is required to prevent telomeric fusions3. 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.
- Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali (DiSTeBA), Università del Salento, Lecce 73100, Italy.
- Istituto di Biologia e Patologia Molecolari del Consiglio Nazionale delle Ricerche (CNR) and Dipartimento di Genetica e Biologia Molecolare, Università di Roma 'La Sapienza', Roma 00185, Italy.
- Molecular Cell and Developmental Biology, University of California, Santa Cruz, California 95064, USA.
- Present address: Dipartimento di Biologia di Base ed Applicata, Università dell'Aquila, L'Aquila 67010, Italy.
Correspondence to: Giovanni Cenci1,4 e-mail: giovanni.cenci@cc.univaq.it
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
RESEARCH
The Drosophila HOAP protein is required for telomere cappingNature Cell Biology Brief Communication (01 Jan 2003)
The role of Drosophila CID in kinetochore formation, cell-cycle progression and heterochromatin interactionsNature Cell Biology Article (01 Aug 2001)
