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From Proteopedia
Cryo-EM structure of CBF1-CCAN bound topologically to centromeric DNA
Structural highlights
FunctionCENPH_YEAST Component of the kinetochore, a multiprotein complex that assembles on centromeric DNA and attaches chromosomes to spindle microtubules, mediating chromosome segregation and sister chromatid segregation during meiosis and mitosis. Component of the inner kinetochore constitutive centromere-associated network (CCAN), which serves as a structural platform for outer kinetochore assembly.[1] Publication Abstract from PubMedThe point centromere of budding yeast specifies assembly of the large kinetochore complex to mediate chromatid segregation. Kinetochores comprise the centromere-associated inner kinetochore (CCAN) complex and the microtubule-binding outer kinetochore KNL1-MIS12-NDC80 (KMN) network. The budding yeast inner kinetochore also contains the DNA binding centromere-binding factor 1 (CBF1) and CBF3 complexes. We determined the cryo-electron microscopy structure of the yeast inner kinetochore assembled onto the centromere-specific centromere protein A nucleosomes (CENP-A(Nuc)). This revealed a central CENP-A(Nuc) with extensively unwrapped DNA ends. These free DNA duplexes bind two CCAN protomers, one of which entraps DNA topologically, positioned on the centromere DNA element I (CDEI) motif by CBF1. The two CCAN protomers are linked through CBF3 forming an arch-like configuration. With a structural mechanism for how CENP-A(Nuc) can also be linked to KMN involving only CENP-QU, we present a model for inner kinetochore assembly onto a point centromere and how it organizes the outer kinetochore for chromosome attachment to the mitotic spindle. Cryo-EM structure of the complete inner kinetochore of the budding yeast point centromere.,Dendooven T, Zhang Z, Yang J, McLaughlin SH, Schwab J, Scheres SHW, Yatskevich S, Barford D Sci Adv. 2023 Jul 28;9(30):eadg7480. doi: 10.1126/sciadv.adg7480. Epub 2023 Jul , 28. PMID:37506202[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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