7r5s
Structure of the human CCAN bound to alpha satellite DNA
Structural highlights
FunctionCENPH_HUMAN Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. Required for chromosome congression and efficiently align the chromosomes on a metaphase plate.[1] [2] [3] Publication Abstract from PubMedKinetochores assemble onto specialized centromeric CENP-A (centromere protein A) nucleosomes (CENP-A(Nuc)) to mediate attachments between chromosomes and the mitotic spindle. We describe cryo-electron microscopy structures of the human inner kinetochore constitutive centromere associated network (CCAN) complex bound to CENP-A(Nuc) reconstituted onto alpha-satellite DNA. CCAN forms edge-on contacts with CENP-A(Nuc), and a linker DNA segment of the alpha-satellite repeat emerges from the fully wrapped end of the nucleosome to thread through the central CENP-LN channel that tightly grips the DNA. The CENP-TWSX histone-fold module further augments DNA binding and partially wraps the linker DNA in a manner reminiscent of canonical nucleosomes. Our study suggests that the topological entrapment of the linker DNA by CCAN provides a robust mechanism by which kinetochores withstand both pushing and pulling forces exerted by the mitotic spindle. Structure of the human inner kinetochore bound to a centromeric CENP-A nucleosome.,Yatskevich S, Muir KW, Bellini D, Zhang Z, Yang J, Tischer T, Predin M, Dendooven T, McLaughlin SH, Barford D Science. 2022 May 20;376(6595):844-852. doi: 10.1126/science.abn3810. Epub 2022 , Apr 14. PMID:35420891[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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