Centromere protein

Function

Centromere proteins (CENP) X,S,W,T make up the kinetochore structure on chromatids where the spindle fibers attach during cell division to pull the chromatids apart.

• CENP-X is a component of the Fanconi Anemia core.
• CENP-B facilitates centromere formation.^[1]
• CENP-A is a component of modified nucleosome replacing hitone H3.^[2]
• CENP-E is a motor protein involved in chromosome movement.^[3]
• CENP-I regulates the recruitment of kinetochore-associated proteins that are required to generate the spindle checkpoint signal.
• CENP-M and CENP-N are involved in the kinetochore assembly.^[4]
• Kinetochore is a complex essential for accurate chromosome segregation.^[5]
• CENP-mis12 from fission yeast is required for correct spindle morphogenesis^[6].

Inner centromere protein (INCENP) is a component of the chromosomal passenger complex which regulates mitosis. INCENP are localized at the centromeres during mid-metaphase of the cell cycle.^[7]

• CBF3 is a yeast complex which interacts with centromeric DNA and mediates nucleosome deposition.^[8]

Disease

CENP-A is overexpressed in colon cancer. A synonymous single nucleotide polymorphism (SNP) in INCENP is associated with breast cancer risk^[9].

Relevance

CENP-B is a potential marker for lung cancer.

Structural highlights

(PDB code 3vh5).^[10]

3D structures of centromere protein

Centromere protein 3D structure

Structure of chicken CENP-X (yellow), CENP-S (cyan), CENP-W (magenta) and CENP-T C-terminal (green) (PDB code 3vh5).

Drag the structure with the mouse to rotate

ReferencesReferences

↑ Tanaka Y, Nureki O, Kurumizaka H, Fukai S, Kawaguchi S, Ikuta M, Iwahara J, Okazaki T, Yokoyama S. Crystal structure of the CENP-B protein-DNA complex: the DNA-binding domains of CENP-B induce kinks in the CENP-B box DNA. EMBO J. 2001 Dec 3;20(23):6612-8. PMID:11726497 doi:10.1093/emboj/20.23.6612
↑ Sekulic N, Bassett EA, Rogers DJ, Black BE. The structure of (CENP-A-H4)(2) reveals physical features that mark centromeres. Nature. 2010 Aug 25. PMID:20739937 doi:10.1038/nature09323
↑ Garcia-Saez I, Blot D, Kahn R, Kozielski F. Crystallization and preliminary crystallographic analysis of the motor domain of human kinetochore-associated protein CENP-E using an automated crystallization procedure. Acta Crystallogr D Biol Crystallogr. 2004 Jun;60(Pt 6):1158-60. Epub 2004, May 21. PMID:15159587 doi:http://dx.doi.org/10.1107/S0907444904009564
↑ Basilico F, Maffini S, Weir JR, Prumbaum D, Rojas AM, Zimniak T, De Antoni A, Jeganathan S, Voss B, van Gerwen S, Krenn V, Massimiliano L, Valencia A, Vetter IR, Herzog F, Raunser S, Pasqualato S, Musacchio A. The pseudo GTPase CENP-M drives human kinetochore assembly. Elife (Cambridge). 2014 Jul 8;3:e02978. doi: 10.7554/eLife.02978. PMID:25006165
↑ Chan GK, Liu ST, Yen TJ. Kinetochore structure and function. Trends Cell Biol. 2005 Nov;15(11):589-98. PMID:16214339 doi:10.1016/j.tcb.2005.09.010
↑ Goshima G, Saitoh S, Yanagida M. Proper metaphase spindle length is determined by centromere proteins Mis12 and Mis6 required for faithful chromosome segregation. Genes Dev. 1999 Jul 1;13(13):1664-77. PMID:10398680
↑ Jeyaprakash AA, Klein UR, Lindner D, Ebert J, Nigg EA, Conti E. Structure of a Survivin-Borealin-INCENP core complex reveals how chromosomal passengers travel together. Cell. 2007 Oct 19;131(2):271-85. PMID:17956729 doi:http://dx.doi.org/10.1016/j.cell.2007.07.045
↑ Yan K, Zhang Z, Yang J, McLaughlin SH, Barford D. Architecture of the CBF3-centromere complex of the budding yeast kinetochore. Nat Struct Mol Biol. 2018 Nov 26. pii: 10.1038/s41594-018-0154-1. doi:, 10.1038/s41594-018-0154-1. PMID:30478265 doi:http://dx.doi.org/10.1038/s41594-018-0154-1
↑ Kabisch M, Lorenzo Bermejo J, Dunnebier T, Ying S, Michailidou K, Bolla MK, Wang Q, Dennis J, Shah M, Perkins BJ, Czene K, Darabi H, Eriksson M, Bojesen SE, Nordestgaard BG, Nielsen SF, Flyger H, Lambrechts D, Neven P, Peeters S, Weltens C, Couch FJ, Olson JE, Wang X, Purrington K, Chang-Claude J, Rudolph A, Seibold P, Flesch-Janys D, Peto J, dos-Santos-Silva I, Johnson N, Fletcher O, Nevanlinna H, Muranen TA, Aittomaki K, Blomqvist C, Schmidt MK, Broeks A, Cornelissen S, Hogervorst FB, Li J, Brand JS, Humphreys K, Guenel P, Truong T, Menegaux F, Sanchez M, Burwinkel B, Marme F, Yang R, Bugert P, Gonzalez-Neira A, Benitez J, Pilar Zamora M, Arias Perez JI, Cox A, Cross SS, Reed MW, Andrulis IL, Knight JA, Glendon G, Tchatchou S, Sawyer EJ, Tomlinson I, Kerin MJ, Miller N, Haiman CA, Schumacher F, Henderson BE, Le Marchand L, Lindblom A, Margolin S, Hooning MJ, Hollestelle A, Kriege M, Koppert LB, Hopper JL, Southey MC, Tsimiklis H, Apicella C, Slettedahl S, Toland AE, Vachon C, Yannoukakos D, Giles GG, Milne RL, McLean C, Fasching PA, Ruebner M, Ekici AB, Beckmann MW, Brenner H, Dieffenbach AK, Arndt V, Stegmaier C, Ashworth A, Orr N, Schoemaker MJ, Swerdlow A, Garcia-Closas M, Figueroa J, Chanock SJ, Lissowska J, Goldberg MS, Labreche F, Dumont M, Winqvist R, Pylkas K, Jukkola-Vuorinen A, Grip M, Brauch H, Bruning T, Ko YD, Radice P, Peterlongo P, Scuvera G, Fortuzzi S, Bogdanova N, Dork T, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, Devilee P, Tollenaar RA, Seynaeve C, Van Asperen CJ, Jakubowska A, Lubinski J, Jaworska-Bieniek K, Durda K, Zheng W, Shrubsole MJ, Cai Q, Torres D, Anton-Culver H, Kristensen V, Bacot F, Tessier DC, Vincent D, Luccarini C, Baynes C, Ahmed S, Maranian M, Simard J, Chenevix-Trench G, Hall P, Pharoah PD, Dunning AM, Easton DF, Hamann U. Inherited variants in the inner centromere protein (INCENP) gene of the chromosomal passenger complex contribute to the susceptibility of ER-negative breast cancer. Carcinogenesis. 2015 Feb;36(2):256-71. doi: 10.1093/carcin/bgu326. Epub 2015 Jan , 13. PMID:25586992 doi:http://dx.doi.org/10.1093/carcin/bgu326
↑ Nishino T, Takeuchi K, Gascoigne KE, Suzuki A, Hori T, Oyama T, Morikawa K, Cheeseman IM, Fukagawa T. CENP-T-W-S-X Forms a Unique Centromeric Chromatin Structure with a Histone-like Fold. Cell. 2012 Feb 3;148(3):487-501. PMID:22304917 doi:10.1016/j.cell.2011.11.061

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Michal Harel, Alexander Berchansky

[1] Tanaka Y, Nureki O, Kurumizaka H, Fukai S, Kawaguchi S, Ikuta M, Iwahara J, Okazaki T, Yokoyama S. Crystal structure of the CENP-B protein-DNA complex: the DNA-binding domains of CENP-B induce kinks in the CENP-B box DNA. EMBO J. 2001 Dec 3;20(23):6612-8. PMID:11726497 doi:10.1093/emboj/20.23.6612

[2] Sekulic N, Bassett EA, Rogers DJ, Black BE. The structure of (CENP-A-H4)(2) reveals physical features that mark centromeres. Nature. 2010 Aug 25. PMID:20739937 doi:10.1038/nature09323

[3] Garcia-Saez I, Blot D, Kahn R, Kozielski F. Crystallization and preliminary crystallographic analysis of the motor domain of human kinetochore-associated protein CENP-E using an automated crystallization procedure. Acta Crystallogr D Biol Crystallogr. 2004 Jun;60(Pt 6):1158-60. Epub 2004, May 21. PMID:15159587 doi:http://dx.doi.org/10.1107/S0907444904009564

[4] Basilico F, Maffini S, Weir JR, Prumbaum D, Rojas AM, Zimniak T, De Antoni A, Jeganathan S, Voss B, van Gerwen S, Krenn V, Massimiliano L, Valencia A, Vetter IR, Herzog F, Raunser S, Pasqualato S, Musacchio A. The pseudo GTPase CENP-M drives human kinetochore assembly. Elife (Cambridge). 2014 Jul 8;3:e02978. doi: 10.7554/eLife.02978. PMID:25006165

[5] Chan GK, Liu ST, Yen TJ. Kinetochore structure and function. Trends Cell Biol. 2005 Nov;15(11):589-98. PMID:16214339 doi:10.1016/j.tcb.2005.09.010

[6] Goshima G, Saitoh S, Yanagida M. Proper metaphase spindle length is determined by centromere proteins Mis12 and Mis6 required for faithful chromosome segregation. Genes Dev. 1999 Jul 1;13(13):1664-77. PMID:10398680

[7] Jeyaprakash AA, Klein UR, Lindner D, Ebert J, Nigg EA, Conti E. Structure of a Survivin-Borealin-INCENP core complex reveals how chromosomal passengers travel together. Cell. 2007 Oct 19;131(2):271-85. PMID:17956729 doi:http://dx.doi.org/10.1016/j.cell.2007.07.045

[8] Yan K, Zhang Z, Yang J, McLaughlin SH, Barford D. Architecture of the CBF3-centromere complex of the budding yeast kinetochore. Nat Struct Mol Biol. 2018 Nov 26. pii: 10.1038/s41594-018-0154-1. doi:, 10.1038/s41594-018-0154-1. PMID:30478265 doi:http://dx.doi.org/10.1038/s41594-018-0154-1

[9] Kabisch M, Lorenzo Bermejo J, Dunnebier T, Ying S, Michailidou K, Bolla MK, Wang Q, Dennis J, Shah M, Perkins BJ, Czene K, Darabi H, Eriksson M, Bojesen SE, Nordestgaard BG, Nielsen SF, Flyger H, Lambrechts D, Neven P, Peeters S, Weltens C, Couch FJ, Olson JE, Wang X, Purrington K, Chang-Claude J, Rudolph A, Seibold P, Flesch-Janys D, Peto J, dos-Santos-Silva I, Johnson N, Fletcher O, Nevanlinna H, Muranen TA, Aittomaki K, Blomqvist C, Schmidt MK, Broeks A, Cornelissen S, Hogervorst FB, Li J, Brand JS, Humphreys K, Guenel P, Truong T, Menegaux F, Sanchez M, Burwinkel B, Marme F, Yang R, Bugert P, Gonzalez-Neira A, Benitez J, Pilar Zamora M, Arias Perez JI, Cox A, Cross SS, Reed MW, Andrulis IL, Knight JA, Glendon G, Tchatchou S, Sawyer EJ, Tomlinson I, Kerin MJ, Miller N, Haiman CA, Schumacher F, Henderson BE, Le Marchand L, Lindblom A, Margolin S, Hooning MJ, Hollestelle A, Kriege M, Koppert LB, Hopper JL, Southey MC, Tsimiklis H, Apicella C, Slettedahl S, Toland AE, Vachon C, Yannoukakos D, Giles GG, Milne RL, McLean C, Fasching PA, Ruebner M, Ekici AB, Beckmann MW, Brenner H, Dieffenbach AK, Arndt V, Stegmaier C, Ashworth A, Orr N, Schoemaker MJ, Swerdlow A, Garcia-Closas M, Figueroa J, Chanock SJ, Lissowska J, Goldberg MS, Labreche F, Dumont M, Winqvist R, Pylkas K, Jukkola-Vuorinen A, Grip M, Brauch H, Bruning T, Ko YD, Radice P, Peterlongo P, Scuvera G, Fortuzzi S, Bogdanova N, Dork T, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, Devilee P, Tollenaar RA, Seynaeve C, Van Asperen CJ, Jakubowska A, Lubinski J, Jaworska-Bieniek K, Durda K, Zheng W, Shrubsole MJ, Cai Q, Torres D, Anton-Culver H, Kristensen V, Bacot F, Tessier DC, Vincent D, Luccarini C, Baynes C, Ahmed S, Maranian M, Simard J, Chenevix-Trench G, Hall P, Pharoah PD, Dunning AM, Easton DF, Hamann U. Inherited variants in the inner centromere protein (INCENP) gene of the chromosomal passenger complex contribute to the susceptibility of ER-negative breast cancer. Carcinogenesis. 2015 Feb;36(2):256-71. doi: 10.1093/carcin/bgu326. Epub 2015 Jan , 13. PMID:25586992 doi:http://dx.doi.org/10.1093/carcin/bgu326

[10] Nishino T, Takeuchi K, Gascoigne KE, Suzuki A, Hori T, Oyama T, Morikawa K, Cheeseman IM, Fukagawa T. CENP-T-W-S-X Forms a Unique Centromeric Chromatin Structure with a Histone-like Fold. Cell. 2012 Feb 3;148(3):487-501. PMID:22304917 doi:10.1016/j.cell.2011.11.061

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