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From Proteopedia
Cryo-EM structure of CBF1-CCAN bound topologically to centromeric DNA
Structural highlights
FunctionCBF1_YEAST Required for chromosome stability and methionine prototrophy. It is involved in chromosomal segregation. Binds to a highly conserved DNA sequence (5'-RTCACRTG-3'), called CDEI, found in centromeres and in several promoters. DNA-binding activity is enhanced by MET28. Required as an auxiliary factor for transcriptional activation of sulfur metabolism together with MET4 and MET28.[1] [2] 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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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