| Structural highlights
Function
CENPO_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. Modulates the kinetochore-bound levels of NDC80 complex.[1] [2] [3] [4]
Publication Abstract from PubMed
In mitosis, accurate chromosome segregation depends on kinetochores that connect centromeric chromatin to spindle microtubules. The centromeres of budding yeast, which are relatively simple, are connected to individual microtubules via a kinetochore constitutive centromere associated network (CCAN). However, the complex centromeres of human chromosomes comprise millions of DNA base pairs and attach to multiple microtubules. Here, by use of cryo-electron microscopy and functional analyses, we reveal the molecular basis of how human CCAN interacts with duplex DNA and facilitates accurate chromosome segregation. The overall structure relates to the cooperative interactions and interdependency of the constituent sub-complexes of the CCAN. The duplex DNA is topologically entrapped by human CCAN. Further, CENP-N does not bind to the RG-loop of CENP-A but to DNA in the CCAN complex. The DNA binding activity is essential for CENP-LN localization to centromere and chromosome segregation during mitosis. Thus, these analyses provide new insights into mechanisms of action underlying kinetochore assembly and function in mitosis.
Structural insights into human CCAN complex assembled onto DNA.,Tian T, Chen L, Dou Z, Yang Z, Gao X, Yuan X, Wang C, Liu R, Shen Z, Gui P, Teng M, Meng X, Hill DL, Li L, Zhang X, Liu X, Sun L, Zang J, Yao X Cell Discov. 2022 Sep 9;8(1):90. doi: 10.1038/s41421-022-00439-6. PMID:36085283[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Okada M, Cheeseman IM, Hori T, Okawa K, McLeod IX, Yates JR 3rd, Desai A, Fukagawa T. The CENP-H-I complex is required for the efficient incorporation of newly synthesized CENP-A into centromeres. Nat Cell Biol. 2006 May;8(5):446-57. Epub 2006 Apr 16. PMID:16622420 doi:http://dx.doi.org/ncb1396
- ↑ Izuta H, Ikeno M, Suzuki N, Tomonaga T, Nozaki N, Obuse C, Kisu Y, Goshima N, Nomura F, Nomura N, Yoda K. Comprehensive analysis of the ICEN (Interphase Centromere Complex) components enriched in the CENP-A chromatin of human cells. Genes Cells. 2006 Jun;11(6):673-84. PMID:16716197 doi:http://dx.doi.org/GTC969
- ↑ McAinsh AD, Meraldi P, Draviam VM, Toso A, Sorger PK. The human kinetochore proteins Nnf1R and Mcm21R are required for accurate chromosome segregation. EMBO J. 2006 Sep 6;25(17):4033-49. doi: 10.1038/sj.emboj.7601293. Epub 2006 Aug , 24. PMID:16932742 doi:http://dx.doi.org/10.1038/sj.emboj.7601293
- ↑ 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
- ↑ Tian T, Chen L, Dou Z, Yang Z, Gao X, Yuan X, Wang C, Liu R, Shen Z, Gui P, Teng M, Meng X, Hill DL, Li L, Zhang X, Liu X, Sun L, Zang J, Yao X. Structural insights into human CCAN complex assembled onto DNA. Cell Discov. 2022 Sep 9;8(1):90. doi: 10.1038/s41421-022-00439-6. PMID:36085283 doi:http://dx.doi.org/10.1038/s41421-022-00439-6
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