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ZW10 links mitotic checkpoint signaling to the structural kinetochore
Open accessAbstract
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.
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KNTC1 demonstrated moderate to strong lethal effects when knocked out in almost every cell line except for those with a KRAS G12V allele.
“the kinetochore-associated protein (KNTC1), a regulator of the mitotic checkpoint70,71, which demonstrated moderate to strong lethal effects when knocked out in almost every cell line except for those with a KRAS G12V allele”
From The origins and genetic interactions of KRAS mutations are allele- and tissue-specific (2021) · cites this paper as [71]
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References 57 · Cited by 249
Research works printed but not linked: 2
- 1997, Methods Enzymol., 283, 572
- 2004, Curr. Biol., 14, 942
Metadata
- Authors
- Kops, G. J. P. L., Kim, Y., Weaver, B. A. A., Mao, Y., McLeod, I., Yates, J. R., Tagaya, M., & Cleveland, D. W.
- Affiliations
- University of California San Diego (US)
- Scripps Research Institute (US)
- Tokyo University of Pharmacy and Life Sciences (JP)
- ORCID
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2005-04-11
- Volume
- 169
- Issue
- 1
- Pages
- 49-60
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC1351127
- OpenAlex
- W2143471239
- Cited by
- 249
- References
- 57
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 9 · 2023: 7 · 2022: 8 · 2021: 6 · 2020: 11 · 2019: 14 · 2018: 21 · 2017: 14 · 2016: 4 · 2015: 18 · 2014: 12 · 2013: 10 · 2012: 10
- FWCI
- 7.18
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R37GM029513, GM 29513, R01GM029513)
- National Center for Research Resources (P41RR011823, RR11823-09)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- ZW10, spindle assembly checkpoint, kinetochore, rods, Mis12 complex, chromosome segregation, chromosomal instability, outer kinetochore
- MeSH terms
- Anaphase, Animals, Chromosomal Proteins, Non-Histone, Female, Flow Cytometry, HeLa Cells, Humans, Microtubule-Associated Proteins, Nuclear Proteins, Oocytes, Xenopus, Genomic Library, Kinetochores, Cell Cycle Proteins, Xenopus Proteins, RNA, Small Interfering, Intracellular Signaling Peptides and Proteins
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