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Mitch a rapidly evolving component of the Ndc80 kinetochore complex required fo...
Williams, Byron; Leung, Garmay; Maiato, Helder; Wong, Alex; Li, ZeXiao; Williams, Erika V.; Kirkpatrick, Catherine; Aquadro, Charles F.We identified an essential kinetochore protein, Mitch, from a genetic screen in D. melanogaster. Mitch localizes to the kinetochore, and its targeting is independent of microtubules (MTs) and several other known kinetochore components. Animals carrying mutations in mitch die as late third-instar larvae; mitotic neuroblasts in larval brains exhibit high levels of aneuploidy. Analysis of fixed D. melanogaster bra...
Mammalian CLASP1 and CLASP2 cooperate to ensure mitotic fidelity by regulating ...
Pereira, Ana L.; Pereira, António J.; Maia, Ana R.R.; Drabek, Ksenija; Sayas, C. Laura; Hergert, Polla J.; Lince-Faria, Mariana; Matos, IrinaCLASPs are widely conserved microtubule plus-end–tracking proteins with essential roles in the local regulation of microtubule dynamics. In yeast, Drosophila, and Xenopus, a single CLASP orthologue is present, which is required for mitotic spindle assembly by regulating microtubule dynamics at the kinetochore. In mammals, however, only CLASP1 has been directly implicated in cell division, despite the existence ...
The ultrastructure of the kinetochore and kinetochore fiber in Drosophila somat...
Maiato, Helder; Hergert, Polla J.; Moutinho-Pereira, Sara; Dong, Yimin; VandenBeldt, Kristin J.; Rieder, Conly L.; McEwen, Bruce F.Drosophila melanogaster is a widely used model organism for the molecular dissection of mitosis in animals. However, despite the popularity of this system, no studies have been published on the ultrastructure of Drosophila kinetochores and kinetochore fibers (K-fibers) in somatic cells. To amend this situation, we used correlative light (LM) and electron microscopy (EM) to study kinetochores in cultured Drosoph...
Drosophila CLASP is required for the incorporation of microtubule subunits into...
Maiato, Helder; Khodjakov, Alexey; Rieder, Conly L.The motion of a chromosome during mitosis is mediated by a bundle of microtubules, termed a kinetochore fibre (K-fibre), which connects the kinetochore of the chromosome to a spindle pole. Once formed, mature K-fibres maintain a steady state length because the continuous addition of microtubule subunits onto microtubule plus ends at the kinetochore is balanced by their removal at their minus ends within the pol...
Kinetochore-driven formation of kinetochore fibers contributes to spindle assem...
Maiato, Helder; Rieder, Conly L.; Khodjakov, AlexeyIt is now clear that a centrosome-independent pathway for mitotic spindle assembly exists even in cells that normally possess centrosomes. The question remains, however, whether this pathway only activates when centrosome activity is compromised, or whether it contributes to spindle morphogenesis during a normal mitosis. Here, we show that many of the kinetochore fibers (K-fibers) in centrosomal Drosophila S2 c...
Stuck in division or passing through: What happens when cells cannot satisfy th...
Rieder, Conly L.; Maiato, HelderThe spindle assembly checkpoint (SAC) delays cells in mitosis when one or more kinetochore(s) cannot form a normal dynamic connection with microtubules (MTs). This occurs when spindle formation fails, or if it forms in the presence of one pole, aberrant centromeres/kinetochores, or MTs exhibiting abnormal dynamics. In the case of spindle poisons, the duration of the delay is influenced by the type of poison, it...
How Do Kinetochores CLASP Dynamic Microtubules?
Maiato, Helder; Rieder, Conly L.; Earnshaw, William C.; Sunkel, Claudio E.Maintenance of genetic stability during cell division requires binding of chromosomes to the mitotic spindle, a process that involves attachment of spindle microtubules to kinetochores. This enables chromosomes to move to the metaphase plate, to satisfy the spindle checkpoint and finally to segregate during anaphase. Recent studies on the function MAST in Drosophila and its human homologue CLASP1, have revealed...
Human CLASP1 is an outer kinetochore component that regulates spindle microtubu...
Maiato, Helder; Rieder, Conly L.; Swedlow, Jason R.; Cole, Richard; Sunkel, Claudio E.; Earnshaw, William C.One of the most intriguing aspects of mitosis is the ability of kinetochores to hold onto the plus-ends of dynamic microtubules that are actively gaining or losing tubulin subunits. Here we show that the microtubule-associated protein CLASP1 is localized preferentially near the plus-ends of growing microtubules during spindle formation and is also a component of a novel region that we term the outer kinetochore...
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