Abstract
The mitotic checkpoint ensures that chromosomes are divided equally between daughter cells and is a primary mechanism preventing the chromosome instability often seen in aneuploid human tumors. ZW10 and Rod play an essential role in this checkpoint. We show that in mitotic human cells ZW10 resides in a complex with Rod and Zwilch, whereas another ZW10 partner, Zwint-1, is part of a separate complex of structural kinetochore components including Mis12 and Ndc80-Hec1. Zwint-1 is critical for recruiting ZW10 to unattached kinetochores. Depletion from human cells or Xenopus egg extracts is used to demonstrate that the ZW10 complex is essential for stable binding of a Mad1-Mad2 complex to unattached kinetochores. Thus, ZW10 functions as a linker between the core structural elements of the outer kinetochore and components that catalyze generation of the mitotic checkpoint-derived "stop anaphase" inhibitor.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Anaphase / genetics
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Anaphase / physiology*
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Animals
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Chromosomal Proteins, Non-Histone / genetics
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Chromosomal Proteins, Non-Histone / metabolism*
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Female
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Flow Cytometry
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Genomic Library
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HeLa Cells
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Humans
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism*
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Kinetochores / physiology*
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Microtubule-Associated Proteins / genetics
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Microtubule-Associated Proteins / metabolism*
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Oocytes / physiology
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RNA, Small Interfering / metabolism
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Xenopus / genetics
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Xenopus / physiology
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Xenopus Proteins / genetics
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Xenopus Proteins / metabolism
Substances
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Cell Cycle Proteins
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Chromosomal Proteins, Non-Histone
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Intracellular Signaling Peptides and Proteins
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Microtubule-Associated Proteins
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Nuclear Proteins
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RNA, Small Interfering
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Xenopus Proteins
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ZW10 protein, human
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ZWINT protein, human