drosophila cenp-a mutations cause a bubr1- dependent early mitotic delay without normal localization of kinetochore components果蝇cenp-a突变导致bubr1u2014u2014依赖早期有丝分裂延迟没有正常的着丝粒的本地化组件.pdfVIP

Drosophila CENP-A Mutations Cause a BubR1- Dependent Early Mitotic Delay without Normal Localization of Kinetochore Components 1 2 3 1,4* Michael D. Blower , Tanya Daigle , Thom Kaufman , Gary H. Karpen 1 Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California, United States of America, 2 Department of Anesthesiology, University of Washington, Seattle, Washington, United States of America, 3 Department of Biology, Indiana University, Bloomington, Indiana, United States of America, 4 Department of Genome Biology, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America The centromere/kinetochore complex plays an essential role in cell and organismal viability by ensuring chromosome movements during mitosis and meiosis. The kinetochore also mediates the spindle attachment checkpoint (SAC), which delays anaphase initiation until all chromosomes have achieved bipolar attachment of kinetochores to the mitotic spindle. CENP-A proteins are centromere-specific chromatin components that provide both a structural and a functional foundation for kinetochore formation. Here we show that cells in Drosophila embryos homozygous for null mutations in CENP-A (CID) display an early mitotic delay. This mitotic delay is not suppressed by inactivation of the DNA damage checkpoint and is unlikely to be the result of DNA damage. Surprisingly, mutation of the SAC component BUBR1 partially suppresses this mitotic delay. Furthermore, cid mutants retain an intact SAC response to spindle disruption despite the inability of many kinetochore proteins, including SAC components, to target to kinetochores. We propose that SAC components are able to monitor spindle assembly and inhibit cell cycle progression in the absence of sustained