期刊
MOLECULAR BIOLOGY OF THE CELL
卷 19, 期 2, 页码 587-594出版社
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E07-10-1051
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- National Institutes of Health [R01-GM074215]
- Ludwig Institute for Cancer Research
- Ministry of Education, Science, Sports, and Culture of Japan
- Jane Coffin Childs Memorial Fund for Medical Research
- Damon Runyon Cancer Research Foundation [DRS 38-04]
Chromosome segregation during mitosis requires the assembly of a large proteinaceous structure termed the kinetochore. In Caenorhabditis elegans, KNL-1 is required to target multiple outer kinetochore proteins. Here, we demonstrate that the vertebrate KNL1 counterpart is essential for chromosome segregation and is required to localize a subset of outer kinetochore proteins. However, unlike in C. elegans, depletion of vertebrate KNL1 does not abolish kinetochore localization of the microtubule-binding Ndc80 complex. Instead, we show that KNL1 and CENP-K, a subunit of a constitutively centromere-associated complex that is missing from C. elegans, coordinately direct Ndc80 complex localization. Simultaneously reducing both hKNL1 and CENP-K function abolishes all aspects of kinetochore assembly downstream of centromeric chromatin and causes catastrophic chromosome segregation defects. These findings explain discrepancies in kinetochore assembly pathways between different organisms and reveal a surprising plasticity in the assembly mechanism of an essential cell division organelle.
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