QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 20, Issue 4, 1252-1267, February 15, 2009

This Article Full Text Full Text (PDF) Supplemental Materials All Versions of this Article: E08-10-1047v1 20/4/1252    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Essex, A. Articles by Desai, A. Search for Related Content PubMed PubMed Citation Articles by Essex, A. Articles by Desai, A.

Systematic Analysis in Caenorhabditis elegans Reveals that the Spindle Checkpoint Is Composed of Two Largely Independent Branches

Anthony Essex^*,, Alexander Dammermann^*, Lindsay Lewellyn^*,, Karen Oegema^*,, and Arshad Desai^*,

*Department of Cellular and Molecular Medicine, Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093; and Biomedical Sciences Graduate Program, School of Medicine, University of California, San Diego, La Jolla, CA 92093

Submitted October 21, 2008; Revised December 3, 2008; Accepted December 5, 2008
Monitoring Editor: Kerry S. Bloom

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 elegans embryo. 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 Mad1^MDF-1/Mad2^MDF-2-based signal, with a largely independent Mad3^SAN-1/BUB-3 pathway. Evidence for independence comes from the fact that subtly elevating Mad2^MDF-2 levels bypasses the requirement for BUB-3 and Mad3^SAN-1 in kinetochore-dependent checkpoint activation. Mad3^SAN-1 does not accumulate at unattached kinetochores and BUB-3 kinetochore localization is independent of Mad2^MDF-2. We discuss the rationale for a bipartite checkpoint mechanism in which a core Mad1^MDF-1/Mad2^MDF-2 signal generated at kinetochores is integrated with a separate cytoplasmic Mad3^SAN-1/BUB-3–based pathway.

Address correspondence to: Arshad Desai (abdesai{at}ucsd.edu).

Abbreviations used: DCON, decondensation; NEBD, nuclear envelope breakdown; OCC, onset of cortical contractility.

This article has been cited by other articles:

				R. Gassmann, A. J. Holland, D. Varma, X. Wan, F. Civril, D. W. Cleveland, K. Oegema, E. D. Salmon, and A. Desai Removal of Spindly from microtubule-attached kinetochores controls spindle checkpoint silencing in human cells Genes & Dev., May 1, 2010; 24(9): 957 - 971. [Abstract] [Full Text] [PDF]

				T. J. Maresca and E. D. Salmon Welcome to a new kind of tension: translating kinetochore mechanics into a wait-anaphase signal J. Cell Sci., March 15, 2010; 123(6): 825 - 835. [Abstract] [Full Text] [PDF]

				V. Vanoosthuyse and K. G. Hardwick Overcoming inhibition in the spindle checkpoint Genes & Dev., December 15, 2009; 23(24): 2799 - 2805. [Abstract] [Full Text] [PDF]