| Structural highlights
Function
CENPH_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 PubMed
Kinetochores 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 Also
References
- ↑ Saffery R, Sumer H, Hassan S, Wong LH, Craig JM, Todokoro K, Anderson M, Stafford A, Choo KH. Transcription within a functional human centromere. Mol Cell. 2003 Aug;12(2):509-16. PMID:14536089 doi:10.1016/s1097-2765(03)00279-x
- ↑ Orthaus S, Ohndorf S, Diekmann S. RNAi knockdown of human kinetochore protein CENP-H. Biochem Biophys Res Commun. 2006 Sep 15;348(1):36-46. PMID:16875666 doi:10.1016/j.bbrc.2006.06.187
- ↑ McClelland SE, Borusu S, Amaro AC, Winter JR, Belwal M, McAinsh AD, Meraldi P. The CENP-A NAC/CAD kinetochore complex controls chromosome congression and spindle bipolarity. EMBO J. 2007 Dec 12;26(24):5033-47. doi: 10.1038/sj.emboj.7601927. Epub 2007 Nov , 15. PMID:18007590 doi:http://dx.doi.org/10.1038/sj.emboj.7601927
- ↑ Yatskevich S, Muir KW, Bellini D, Zhang Z, Yang J, Tischer T, Predin M, Dendooven T, McLaughlin SH, Barford D. Structure of the human inner kinetochore bound to a centromeric CENP-A nucleosome. Science. 2022 May 20;376(6595):844-852. PMID:35420891 doi:10.1126/science.abn3810
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