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The human Mis12 complex is required for kinetochore assembly and proper chromosome segregation
Open accessAbstract
During cell division, kinetochores form the primary chromosomal attachment sites for spindle microtubules. We previously identified a network of 10 interacting kinetochore proteins conserved between Caenorhabditis elegans and humans. In this study, we investigate three proteins in the human network (hDsn1Q9H410, hNnf1PMF1, and hNsl1DC31). Using coexpression in bacteria and fractionation of mitotic extracts, we demonstrate that these proteins form a stable complex with the conserved kinetochore component hMis12. Human or chicken cells depleted of Mis12 complex subunits are delayed in mitosis with misaligned chromosomes and defects in chromosome biorientation. Aligned chromosomes exhibited reduced centromere stretch and diminished kinetochore microtubule bundles. Consistent with this, localization of the outer plate constituent Ndc80HEC1 was severely reduced. The checkpoint protein BubR1, the fibrous corona component centromere protein (CENP) E, and the inner kinetochore proteins CENP-A and CENP-H also failed to accumulate to wild-type levels in depleted cells. These results indicate that a four-subunit Mis12 complex plays an essential role in chromosome segregation in vertebrates and contributes to mitotic kinetochore assembly.
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Citations
Cited by
Molecular architecture of the kinetochore–microtubule interface
Cheeseman, I. M., & Desai, A. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2310 · Cited by 915
Self-citationA Molecular View of Kinetochore Assembly and Function
Musacchio, A., & Desai, A. (2017) · Biology · doi:10.3390/biology6010005 · Cited by 544
Self-citationPriming of Centromere for CENP-A Recruitment by Human hMis18α, hMis18β, and M18BP1
Fujita, Y., Hayashi, T., Kiyomitsu, T., Toyoda, Y., Kokubu, A., Obuse, C., & Yanagida, M. (2007) · Developmental Cell · doi:10.1016/j.devcel.2006.11.002 · Cited by 398
Foley, E. A., Maldonado, M., & Kapoor, T. M. (2011) · Nature Cell Biology · doi:10.1038/ncb2327 · Cited by 267
Kinetochore KMN network gene CASC5 mutated in primary microcephaly
Genin, A., Desir, J., Lambert, N., Biervliet, M., Van Der Aa, N., Pierquin, G., Killian, A., Tosi, M., Urbina, M., Lefort, A., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds386 · Cited by 116
Metadata
- Authors
- Kline, S. L., Cheeseman, I. M., Hori, T., Fukagawa, T., & Desai, A.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2006-04-03
- Volume
- 173
- Issue
- 1
- Pages
- 9-17
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2099761749
- Cited by
- 213
- References
- 0
- FWCI
- 6.99
- Type
- journal article
- Language
- en
- Open access
- green
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- Kline, S. L., Cheeseman, I. M., Hori, T., Fukagawa, T., & Desai, A. (2006). The human Mis12 complex is required for kinetochore assembly and proper chromosome segregation. The Journal of Cell Biology. https://doi.org/10.1083/jcb.200509158
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