| Structural highlights
Function
[NSL1_HUMAN] Part of the MIS12 complex which is required for normal chromosome alignment and segregation and kinetochore formation during mitosis.[1] [MIS12_HUMAN] Part of the MIS12 complex which is required for normal chromosome alignment and segregation and for kinetochore formation during mitosis (PubMed:12515822, PubMed:15502821, PubMed:16585270). Essential for proper kinetochore microtubule attachments (PubMed:23891108).[2] [3] [4] [5] [DSN1_HUMAN] Part of the MIS12 complex which is required for normal chromosome alignment and segregation and kinetochore formation during mitosis.[6] [7] [PMF1_HUMAN] Part of the MIS12 complex which is required for normal chromosome alignment and segregation and kinetochore formation during mitosis. May act as a cotranscription partner of NFE2L2 involved in regulation of polyamine-induced transcription of SSAT.[8] [9] [10] [11] [CENPC_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. CENPC recruits DNA methylation and DNMT3B to both centromeric and pericentromeric satellite repeats and regulates the histone code in these regions.[12] [13]
Publication Abstract from PubMed
Kinetochores, multisubunit protein assemblies, connect chromosomes to spindle microtubules to promote chromosome segregation. The 10-subunit KMN assembly (comprising KNL1, MIS12, and NDC80 complexes, designated KNL1C, MIS12C, and NDC80C) binds microtubules and regulates mitotic checkpoint function through NDC80C and KNL1C, respectively. MIS12C, on the other hand, connects the KMN to the chromosome-proximal domain of the kinetochore through a direct interaction with CENP-C. The structural basis for this crucial bridging function of MIS12C is unknown. Here, we report crystal structures of human MIS12C associated with a fragment of CENP-C and unveil the role of Aurora B kinase in the regulation of this interaction. The structure of MIS12:CENP-C complements previously determined high-resolution structures of functional regions of NDC80C and KNL1C and allows us to build a near-complete structural model of the KMN assembly. Our work illuminates the structural organization of essential chromosome segregation machinery that is conserved in most eukaryotes.
Structure of the MIS12 Complex and Molecular Basis of Its Interaction with CENP-C at Human Kinetochores.,Petrovic A, Keller J, Liu Y, Overlack K, John J, Dimitrova YN, Jenni S, van Gerwen S, Stege P, Wohlgemuth S, Rombaut P, Herzog F, Harrison SC, Vetter IR, Musacchio A Cell. 2016 Nov 3;167(4):1028-1040.e15. doi: 10.1016/j.cell.2016.10.005. Epub 2016, Oct 27. PMID:27881301[14]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kline SL, Cheeseman IM, Hori T, Fukagawa T, Desai A. The human Mis12 complex is required for kinetochore assembly and proper chromosome segregation. J Cell Biol. 2006 Apr 10;173(1):9-17. Epub 2006 Apr 3. PMID:16585270 doi:http://dx.doi.org/10.1083/jcb.200509158
- ↑ Goshima G, Kiyomitsu T, Yoda K, Yanagida M. Human centromere chromatin protein hMis12, essential for equal segregation, is independent of CENP-A loading pathway. J Cell Biol. 2003 Jan 6;160(1):25-39. Epub 2003 Jan 6. PMID:12515822 doi:http://dx.doi.org/10.1083/jcb.200210005
- ↑ Obuse C, Iwasaki O, Kiyomitsu T, Goshima G, Toyoda Y, Yanagida M. A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1. Nat Cell Biol. 2004 Nov;6(11):1135-41. Epub 2004 Oct 24. PMID:15502821 doi:http://dx.doi.org/10.1038/ncb1187
- ↑ Kline SL, Cheeseman IM, Hori T, Fukagawa T, Desai A. The human Mis12 complex is required for kinetochore assembly and proper chromosome segregation. J Cell Biol. 2006 Apr 10;173(1):9-17. Epub 2006 Apr 3. PMID:16585270 doi:http://dx.doi.org/10.1083/jcb.200509158
- ↑ Shrestha RL, Draviam VM. Lateral to end-on conversion of chromosome-microtubule attachment requires kinesins CENP-E and MCAK. Curr Biol. 2013 Aug 19;23(16):1514-26. doi: 10.1016/j.cub.2013.06.040. Epub 2013 , Jul 25. PMID:23891108 doi:http://dx.doi.org/10.1016/j.cub.2013.06.040
- ↑ Obuse C, Iwasaki O, Kiyomitsu T, Goshima G, Toyoda Y, Yanagida M. A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1. Nat Cell Biol. 2004 Nov;6(11):1135-41. Epub 2004 Oct 24. PMID:15502821 doi:http://dx.doi.org/10.1038/ncb1187
- ↑ Kline SL, Cheeseman IM, Hori T, Fukagawa T, Desai A. The human Mis12 complex is required for kinetochore assembly and proper chromosome segregation. J Cell Biol. 2006 Apr 10;173(1):9-17. Epub 2006 Apr 3. PMID:16585270 doi:http://dx.doi.org/10.1083/jcb.200509158
- ↑ Wang Y, Devereux W, Stewart TM, Casero RA Jr. Cloning and characterization of human polyamine-modulated factor-1, a transcriptional cofactor that regulates the transcription of the spermidine/spermine N(1)-acetyltransferase gene. J Biol Chem. 1999 Jul 30;274(31):22095-101. PMID:10419538
- ↑ Wang Y, Devereux W, Stewart TM, Casero RA Jr. Characterization of the interaction between the transcription factors human polyamine modulated factor (PMF-1) and NF-E2-related factor 2 (Nrf-2) in the transcriptional regulation of the spermidine/spermine N1-acetyltransferase (SSAT) gene. Biochem J. 2001 Apr 1;355(Pt 1):45-9. PMID:11256947
- ↑ Obuse C, Iwasaki O, Kiyomitsu T, Goshima G, Toyoda Y, Yanagida M. A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1. Nat Cell Biol. 2004 Nov;6(11):1135-41. Epub 2004 Oct 24. PMID:15502821 doi:http://dx.doi.org/10.1038/ncb1187
- ↑ Kline SL, Cheeseman IM, Hori T, Fukagawa T, Desai A. The human Mis12 complex is required for kinetochore assembly and proper chromosome segregation. J Cell Biol. 2006 Apr 10;173(1):9-17. Epub 2006 Apr 3. PMID:16585270 doi:http://dx.doi.org/10.1083/jcb.200509158
- ↑ Gopalakrishnan S, Sullivan BA, Trazzi S, Della Valle G, Robertson KD. DNMT3B interacts with constitutive centromere protein CENP-C to modulate DNA methylation and the histone code at centromeric regions. Hum Mol Genet. 2009 Sep 1;18(17):3178-93. doi: 10.1093/hmg/ddp256. Epub 2009 May , 29. PMID:19482874 doi:http://dx.doi.org/10.1093/hmg/ddp256
- ↑ Gascoigne KE, Takeuchi K, Suzuki A, Hori T, Fukagawa T, Cheeseman IM. Induced ectopic kinetochore assembly bypasses the requirement for CENP-A nucleosomes. Cell. 2011 Apr 29;145(3):410-22. doi: 10.1016/j.cell.2011.03.031. PMID:21529714 doi:http://dx.doi.org/10.1016/j.cell.2011.03.031
- ↑ Petrovic A, Keller J, Liu Y, Overlack K, John J, Dimitrova YN, Jenni S, van Gerwen S, Stege P, Wohlgemuth S, Rombaut P, Herzog F, Harrison SC, Vetter IR, Musacchio A. Structure of the MIS12 Complex and Molecular Basis of Its Interaction with CENP-C at Human Kinetochores. Cell. 2016 Nov 3;167(4):1028-1040.e15. doi: 10.1016/j.cell.2016.10.005. Epub 2016, Oct 27. PMID:27881301 doi:http://dx.doi.org/10.1016/j.cell.2016.10.005
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