{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yatskevich S"],"funding":["Cancer Research UK","Medical Research Council"],"pagination":["844-852"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7612757"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["376(6595)"],"pubmed_abstract":["Kinetochores assemble onto specialized centromeric CENP-A (centromere protein A) nucleosomes (CENP-A<sup>Nuc</sup>) 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<sup>Nuc</sup> reconstituted onto α-satellite DNA. CCAN forms edge-on contacts with CENP-A<sup>Nuc</sup>, and a linker DNA segment of the α-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."],"journal":["Science (New York, N.Y.)"],"pubmed_title":["Structure of the human inner kinetochore bound to a centromeric CENP-A nucleosome."],"pmcid":["PMC7612757"],"funding_grant_id":["24307","MC_UP_1201/6","DRCRPG-Jun22\\100004","MC_U105184326"],"pubmed_authors":["Tischer T","Yang J","Predin M","Zhang Z","Bellini D","Yatskevich S","Muir KW","McLaughlin SH","Dendooven T","Barford D"],"additional_accession":[]},"is_claimable":false,"name":"Structure of the human inner kinetochore bound to a centromeric CENP-A nucleosome.","description":"Kinetochores assemble onto specialized centromeric CENP-A (centromere protein A) nucleosomes (CENP-A<sup>Nuc</sup>) 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<sup>Nuc</sup> reconstituted onto α-satellite DNA. CCAN forms edge-on contacts with CENP-A<sup>Nuc</sup>, and a linker DNA segment of the α-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.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 May","modification":"2025-04-04T02:25:24.342Z","creation":"2025-02-19T01:23:40.299Z"},"accession":"S-EPMC7612757","cross_references":{"pubmed":["35420891"],"doi":["10.1126/science.abn3810"]}}