Kinetochores, multisubunit protein assemblies, connect chromosomes to spindle microtubules to promote chromosome segregation. The 10-subunit KMN assembly (comprising KNL1, MIS12, and NDC80 complexes, designated KNL1C, MIS12C, and NDC80C) binds microtubules and regulates mitotic checkpoint function through NDC80C and KNL1C, respectively. MIS12C, on the other hand, connects the KMN to the chromosome-proximal domain of the kinetochore through a direct interaction with CENP-C. The structural basis for this crucial bridging function of MIS12C is unknown. Here, we report crystal structures of human MIS12C associated with a fragment of CENP-C and unveil the role of Aurora B kinase in the regulation of this interaction. The structure of MIS12:CENP-C complements previously determined high-resolution structures of functional regions of NDC80C and KNL1C and allows us to build a near-complete structural model of the KMN assembly. Our work illuminates the structural organization of essential chromosome segregation machinery that is conserved in most eukaryotes.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5101189 | PMC |
| http://dx.doi.org/10.1016/j.cell.2016.10.005 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Centromeric localization of αKNL2 and CENP-C proteins in plants depends on their centromere-targeting domain and DNA-binding regions.
Nucleic Acids Res
December 2024
Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) OT Gatersleben, Corrensstr 3, 06466 Seeland, Germany.
In eukaryotes, accurate chromosome segregation during cell division relies on the centromeric histone H3 variant, CENH3. Our previous work identified KINETOCHORE NULL2 (αKNL2) as a plant CENH3 assembly factor, which contains a centromere-targeting motif, CENPC-k, analogous to the CENPC motif found in CENP-C. We also demonstrated that αKNL2 can bind DNA in vitro in a sequence-independent manner, without the involvement of its CENPC-k motif.
View Article and Find Full Text PDFMolecular details and phosphoregulation of the CENP-T-Mis12 complex interaction during mitosis in DT40 cells.
iScience
December 2024
Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
To establish bipolar attachments of microtubules to sister chromatids, an inner kinetochore subcomplex, the constitutive centromere-associated network (CCAN), is assembled on centromeric chromatin and recruits the microtubule-binding subcomplex called the KMN network. Since CCAN proteins CENP-C and CENP-T independently bind to the Mis12 complex (Mis12C) of KMN, it is difficult to evaluate the significance of each interaction in cells. Here, we demonstrate the molecular details of the CENP-T-Mis12C interaction using chicken DT40 cells lacking the CENP-C-Mis12C interaction.
View Article and Find Full Text PDFPlant kinetochore complex: composition, function, and regulation.
Front Plant Sci
October 2024
Guangdong Provincial Key Laboratory for Plant Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China.
The kinetochore complex, an important protein assembly situated on the centromere, plays a pivotal role in chromosome segregation during cell division. Like in animals and fungi, the plant kinetochore complex is important for maintaining chromosome stability, regulating microtubule attachment, executing error correction mechanisms, and participating in signaling pathways to ensure accurate chromosome segregation. This review summarizes the composition, function, and regulation of the plant kinetochore complex, emphasizing the interactions of kinetochore proteins with centromeric DNAs (cenDNAs) and RNAs (cenRNAs).
View Article and Find Full Text PDFCENP-C-Mis12 complex establishes a regulatory loop through Aurora B for chromosome segregation.
Life Sci Alliance
January 2025
Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan
Establishing the correct kinetochore-microtubule attachment is crucial for faithful chromosome segregation. The kinetochore has various regulatory mechanisms for establishing correct bipolar attachment. However, how the regulations are coupled is not fully understood.
View Article and Find Full Text PDFCENP-C-targeted PLK-1 regulates kinetochore function in C. elegans embryos.
J Cell Sci
November 2024
Molecular, Cellular and Developmental Biology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Polo-like kinase 1 (PLK-1) is present in centrosomes, the nuclear envelope and kinetochores and plays a significant role in meiosis and mitosis. PLK-1 depletion or inhibition has severe consequences for spindle assembly, spindle assembly checkpoint (SAC) activation, chromosome segregation and cytokinesis. BUB-1 targets PLK-1 to the outer kinetochore and, in mammals, the inner kinetochore PLK1 targeting is mediated by the constitutive centromere associated network (CCAN).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!