Structural highlights
FunctionCENPL_HUMAN Component of the CENPA-CAD (nucleosome distal) complex, a complex recruited to centromeres which is involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation. May be involved in incorporation of newly synthesized CENPA into centromeres via its interaction with the CENPA-NAC complex.[1] 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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