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Systematic Analysis in Caenorhabditis elegansReveals that the Spindle Checkpoint Is Composed of Two Largely Independent Branches
- Source :
- Molecular Biology of the Cell; February 2009, Vol. 20 Issue: 4 p1252-1267, 16p
- Publication Year :
- 2009
-
Abstract
- Kinetochores use the spindle checkpoint to delay anaphase onset until all chromosomes have formed bipolar attachments to spindle microtubules. Here, we use controlled monopolar spindle formation to systematically define the requirements for spindle checkpoint signaling in the Caenorhabditis elegansembryo. The results, when interpreted in light of kinetochore assembly epistasis analysis, indicate that checkpoint activation is coordinately directed by the NDC-80 complex, the Rod/Zwilch/Zw10 complex, and BUB-1—three components independently targeted to the outer kinetochore by the scaffold protein KNL-1. These components orchestrate the integration of a core Mad1MDF-1/Mad2MDF-2-based signal, with a largely independent Mad3SAN-1/BUB-3 pathway. Evidence for independence comes from the fact that subtly elevating Mad2MDF-2levels bypasses the requirement for BUB-3 and Mad3SAN-1in kinetochore-dependent checkpoint activation. Mad3SAN-1does not accumulate at unattached kinetochores and BUB-3 kinetochore localization is independent of Mad2MDF-2. We discuss the rationale for a bipartite checkpoint mechanism in which a core Mad1MDF-1/Mad2MDF-2signal generated at kinetochores is integrated with a separate cytoplasmic Mad3SAN-1/BUB-3–based pathway.
Details
- Language :
- English
- ISSN :
- 10591524 and 19394586
- Volume :
- 20
- Issue :
- 4
- Database :
- Supplemental Index
- Journal :
- Molecular Biology of the Cell
- Publication Type :
- Periodical
- Accession number :
- ejs46606379
- Full Text :
- https://doi.org/10.1091/mbc.e08-10-1047