A mitotic role for Mad1 beyond the spindle checkpoint
| Autor: | Régine Terracol, Zohra Rahmani, Anaïs Poncet, Roger E. Karess, Doruk Emre |
|---|---|
| Přispěvatelé: | Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Association pour la Recherche sur le Cancer (ARC). Ministère de l'Enseignement supérieur et de la Recherche and La Fondation pour la Recherche Medicale |
| Rok vydání: | 2011 |
| Předmět: |
Mad2
Mad1 Transgene Green Fluorescent Proteins Mitosis Cell Cycle Proteins [SDV.BC]Life Sciences [q-bio]/Cellular Biology Spindle Apparatus Biology Spindle assembly checkpoint RZZ 03 medical and health sciences Animals Drosophila Proteins Transgenes Kinetochores 030304 developmental biology Anaphase 0303 health sciences Kinetochore 030302 biochemistry & molecular biology Dynein Nuclear Proteins Cell Biology Cell biology Spindle checkpoint Anaphase lag Phenotype Mad2 Proteins Mutation Drosophila Signal Transduction |
| Zdroj: | Journal of Cell Science Journal of Cell Science, Company of Biologists, 2011, 124 (Pt 10), pp.1664-71. ⟨10.1242/jcs.081216⟩ |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.081216 |
| Popis: | International audience; Unattached kinetochores generate an anaphase inhibitor, through the spindle assembly checkpoint (SAC), that allows cells more time to establish proper kinetochore-microtubule (K-MT) linkages and thus avoid aneuploidy. Mad1 is the receptor for Mad2 at kinetochores, where it catalyzes the formation of Mad2-Cdc20 complexes, an essential part of the anaphase inhibitor, but whether it has any other mitotic function is unknown. We have generated a mad1-null mutation in Drosophila. This mutant is SAC defective and Mad2 is no longer localized to either nuclear envelope or kinetochores, but it displays normal basal mitotic timing. Unlike mad2 mutants, which have relatively normal mitoses, mad1 anaphases show high frequencies of lagging chromatids, at least some of which are caused by persistent merotelic linkages. A transgene expressing GFP-Mad1 rescues both the SAC and the anaphase defects. In an attempt to separate the SAC function from the mitotic function, we made a mad1 transgene with a mutated Mad2-binding domain. Surprisingly, this transgene failed to complement the anaphase phenotype. Thus, Mad1 has activity promoting proper K-MT attachments in addition to its checkpoint function. This activity does not require the presence of Mad2, but it does depend in some unknown way on key residues in the Mad2-binding domain of Mad1. |
| Databáze: | OpenAIRE |
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