| Structural highlights6qld is a 22 chain structure with sequence from [1] and Baker's yeast. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Gene: | MIF2, YKL089W (Baker's yeast), CTF19, MCM18, YPL018W, LPB13W (Baker's yeast), OKP1, YGR179C (Baker's yeast), AME1, ARP100, YBR211C, YBR1458 (Baker's yeast), NKP1, YDR383C (Baker's yeast), NKP2, YLR315W (Baker's yeast), CSE4, CSL2, YKL049C, YKL262 (Baker's yeast), HHF1, YBR009C, YBR0122, HHF2, YNL030W, N2752 (Baker's yeast), HTB2, H2B2, YBL002W, YBL0104 (Baker's yeast), HTA1, H2A1, SPT11, YDR225W, YD9934.10 (Baker's yeast), HTB1, H2B1, SPT12, YDR224C, YD9934.09C (Baker's yeast), MCM16, YPR046W (Baker's yeast), CTF3, CHL3, YLR381W (Baker's yeast), MCM22, YJR135C, J2122 (Baker's yeast), IML3, MCM19, YBR107C, YBR0836 (Baker's yeast), CHL4, CTF17, MCM17, YDR254W, YD9320A.04 (Baker's yeast), MCM21, CTF5, YDR318W (Baker's yeast) |
| Experimental data: | Check | | Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function[CENPQ_YEAST] Component of the kinetochore, a multiprotein complex that assembles on centromeric DNA and attaches chromosomes to spindle microtubules, mediating chromosome segregation and sister chromatid segregation during meiosis and mitosis. Component of the inner kinetochore COMA complex, which connects centromere-associated proteins and the outer kinetochore. COMA interacts with other inner kinetochore proteins to form the inner kinetochore constitutive centromere-associated network (CCAN), which serves as a structural platform for outer kinetochore assembly.[1] [2] [H2A1_YEAST] Core component of nucleosome which plays a central role in DNA double strand break (DSB) repair. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.[3] [4] [5] [6] [CENPL_YEAST] Component of the kinetochore, a multiprotein complex that assembles on centromeric DNA and attaches chromosomes to spindle microtubules, mediating chromosome segregation and sister chromatid segregation during meiosis and mitosis. Component of the inner kinetochore constitutive centromere-associated network (CCAN), which serves as a structural platform for outer kinetochore assembly.[7] [8] [H2B2_YEAST] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.[9] [10] [11] [12] [13] [14] [15] [CENPC_YEAST] Component of the kinetochore, a multiprotein complex that assembles on centromeric DNA and attaches chromosomes to spindle microtubules, mediating chromosome segregation and sister chromatid segregation during meiosis and mitosis. Component of the inner kinetochore constitutive centromere-associated network (CCAN), which serves as a structural platform for outer kinetochore assembly (PubMed:8408221, PubMed:7579695, PubMed:22561346).[16] [17] [18] [CENPA_YEAST] Histone H3-like variant which exclusively replaces conventional H3 in the nucleosome core of centromeric chromatin at the inner plate of the kinetochore. Required for recruitment and assembly of kinetochore proteins, mitotic progression and chromosome segregation. May serve as an epigenetic mark that propagates centromere identity through replication and cell division. Required for functional chromatin architecture at the yeast 2-micron circle partitioning locus and promotes equal plasmid segregation.[19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [NKP1_YEAST] Component of the kinetochore, a multiprotein complex that assembles on centromeric DNA and attaches chromosomes to spindle microtubules, mediating chromosome segregation and sister chromatid segregation during meiosis and mitosis. Component of the inner kinetochore constitutive centromere-associated network (CCAN), which serves as a structural platform for outer kinetochore assembly.[30] [CENPK_YEAST] Component of the kinetochore, a multiprotein complex that assembles on centromeric DNA and attaches chromosomes to spindle microtubules, mediating chromosome segregation and sister chromatid segregation during meiosis and mitosis. Component of the inner kinetochore constitutive centromere-associated network (CCAN), which serves as a structural platform for outer kinetochore assembly.[31] [CENPH_YEAST] Component of the kinetochore, a multiprotein complex that assembles on centromeric DNA and attaches chromosomes to spindle microtubules, mediating chromosome segregation and sister chromatid segregation during meiosis and mitosis. Component of the inner kinetochore constitutive centromere-associated network (CCAN), which serves as a structural platform for outer kinetochore assembly.[32] [CENPO_YEAST] Component of the kinetochore, a multiprotein complex that assembles on centromeric DNA and attaches chromosomes to spindle microtubules, mediating chromosome segregation and sister chromatid segregation during meiosis and mitosis. Component of the inner kinetochore COMA complex, which connects centromere-associated proteins and the outer kinetochore. COMA interacts with other inner kinetochore proteins to form the inner kinetochore constitutive centromere-associated network (CCAN), which serves as a structural platform for outer kinetochore assembly.[33] [CENPU_YEAST] Component of the kinetochore, a multiprotein complex that assembles on centromeric DNA and attaches chromosomes to spindle microtubules, mediating chromosome segregation and sister chromatid segregation during meiosis and mitosis. Component of the inner kinetochore COMA complex, which connects centromere-associated proteins and the outer kinetochore. COMA interacts with other inner kinetochore proteins to form the inner kinetochore constitutive centromere-associated network (CCAN), which serves as a structural platform for outer kinetochore assembly.[34] [NKP2_YEAST] Component of the kinetochore, a multiprotein complex that assembles on centromeric DNA and attaches chromosomes to spindle microtubules, mediating chromosome segregation and sister chromatid segregation during meiosis and mitosis. Component of the inner kinetochore constitutive centromere-associated network (CCAN), which serves as a structural platform for outer kinetochore assembly.[35] [H2B1_YEAST] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.[36] [37] [38] [39] [40] [41] [42] [43] [44] [CENPN_YEAST] Component of the kinetochore, a multiprotein complex that assembles on centromeric DNA and attaches chromosomes to spindle microtubules, mediating chromosome segregation and sister chromatid segregation during meiosis and mitosis. Component of the inner kinetochore constitutive centromere-associated network (CCAN), which serves as a structural platform for outer kinetochore assembly.[45] [CENPI_YEAST] Component of the central kinetochore, which mediates the attachment of the centromere to the mitotic spindle by forming essential interactions between the microtubule-associated outer kinetochore proteins and the centromere-associated inner kinetochore proteins. Required for establishing bipolar spindle-microtubule attachments and proper chromosome segregation. Component of the kinetochore, a multiprotein complex that assembles on centromeric DNA and attaches chromosomes to spindle microtubules, mediating chromosome segregation and sister chromatid segregation during meiosis and mitosis. Component of the inner kinetochore constitutive centromere-associated network (CCAN), which serves as a structural platform for outer kinetochore assembly.[46] [CENPP_YEAST] Component of the kinetochore, a multiprotein complex that assembles on centromeric DNA and attaches chromosomes to spindle microtubules, mediating chromosome segregation and sister chromatid segregation during meiosis and mitosis. Component of the inner kinetochore COMA complex, which connects centromere-associated proteins and the outer kinetochore. COMA interacts with other inner kinetochore proteins to form the inner kinetochore constitutive centromere-associated network (CCAN), which serves as a structural platform for outer kinetochore assembly.[47] [48]
Publication Abstract from PubMed
In eukaryotes, accurate chromosome segregation in mitosis and meiosis maintains genome stability and prevents aneuploidy. Kinetochores are large protein complexes that, by assembling onto specialized Cenp-A nucleosomes(1,2), function to connect centromeric chromatin to microtubules of the mitotic spindle(3,4). Whereas the centromeres of vertebrate chromosomes comprise millions of DNA base pairs and attach to multiple microtubules, the simple point centromeres of budding yeast are connected to individual microtubules(5,6). All 16 budding yeast chromosomes assemble complete kinetochores using a single Cenp-A nucleosome (Cenp-A(Nuc)), each of which is perfectly centred on its cognate centromere(7-9). The inner and outer kinetochore modules are responsible for interacting with centromeric chromatin and microtubules, respectively. Here we describe the cryo-electron microscopy structure of the Saccharomyces cerevisiae inner kinetochore module, the constitutive centromere associated network (CCAN) complex, assembled onto a Cenp-A nucleosome (CCAN-Cenp-A(Nuc)). The structure explains the interdependency of the constituent subcomplexes of CCAN and shows how the Y-shaped opening of CCAN accommodates Cenp-A(Nuc) to enable specific CCAN subunits to contact the nucleosomal DNA and histone subunits. Interactions with the unwrapped DNA duplex at the two termini of Cenp-A(Nuc) are mediated predominantly by a DNA-binding groove in the Cenp-L-Cenp-N subcomplex. Disruption of these interactions impairs assembly of CCAN onto Cenp-A(Nuc). Our data indicate a mechanism of Cenp-A nucleosome recognition by CCAN and how CCAN acts as a platform for assembly of the outer kinetochore to link centromeres to the mitotic spindle for chromosome segregation.
Structure of the inner kinetochore CCAN complex assembled onto a centromeric nucleosome.,Yan K, Yang J, Zhang Z, McLaughlin SH, Chang L, Fasci D, Ehrenhofer-Murray AE, Heck AJR, Barford D Nature. 2019 Oct 2. pii: 10.1038/s41586-019-1609-1. doi:, 10.1038/s41586-019-1609-1. PMID:31578520[49]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
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- ↑ De Wulf P, McAinsh AD, Sorger PK. Hierarchical assembly of the budding yeast kinetochore from multiple subcomplexes. Genes Dev. 2003 Dec 1;17(23):2902-21. Epub 2003 Nov 21. PMID:14633972 doi:http://dx.doi.org/10.1101/gad.1144403
- ↑ Downs JA, Lowndes NF, Jackson SP. A role for Saccharomyces cerevisiae histone H2A in DNA repair. Nature. 2000 Dec 21-28;408(6815):1001-4. PMID:11140636 doi:10.1038/35050000
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- ↑ Ghosh SK, Sau S, Lahiri S, Lohia A, Sinha P. The Iml3 protein of the budding yeast is required for the prevention of precocious sister chromatid separation in meiosis I and for sister chromatid disjunction in meiosis II. Curr Genet. 2004 Aug;46(2):82-91. Epub 2004 Jul 6. PMID:15241623 doi:http://dx.doi.org/10.1007/s00294-004-0516-6
- ↑ Briggs SD, Xiao T, Sun ZW, Caldwell JA, Shabanowitz J, Hunt DF, Allis CD, Strahl BD. Gene silencing: trans-histone regulatory pathway in chromatin. Nature. 2002 Aug 1;418(6897):498. Epub 2002 Jul 14. PMID:12152067 doi:10.1038/nature00970
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- ↑ Yamashita K, Shinohara M, Shinohara A. Rad6-Bre1-mediated histone H2B ubiquitylation modulates the formation of double-strand breaks during meiosis. Proc Natl Acad Sci U S A. 2004 Aug 3;101(31):11380-5. Epub 2004 Jul 27. PMID:15280549 doi:10.1073/pnas.0400078101
- ↑ Ahn SH, Cheung WL, Hsu JY, Diaz RL, Smith MM, Allis CD. Sterile 20 kinase phosphorylates histone H2B at serine 10 during hydrogen peroxide-induced apoptosis in S. cerevisiae. Cell. 2005 Jan 14;120(1):25-36. PMID:15652479 doi:S009286740401092X
- ↑ Ahn SH, Henderson KA, Keeney S, Allis CD. H2B (Ser10) phosphorylation is induced during apoptosis and meiosis in S. cerevisiae. Cell Cycle. 2005 Jun;4(6):780-3. Epub 2005 Jun 14. PMID:15970663
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- ↑ Schleiffer A, Maier M, Litos G, Lampert F, Hornung P, Mechtler K, Westermann S. CENP-T proteins are conserved centromere receptors of the Ndc80 complex. Nat Cell Biol. 2012 May 6;14(6):604-13. doi: 10.1038/ncb2493. PMID:22561346 doi:http://dx.doi.org/10.1038/ncb2493
- ↑ Meluh PB, Koshland D. Evidence that the MIF2 gene of Saccharomyces cerevisiae encodes a centromere protein with homology to the mammalian centromere protein CENP-C. Mol Biol Cell. 1995 Jul;6(7):793-807. doi: 10.1091/mbc.6.7.793. PMID:7579695 doi:http://dx.doi.org/10.1091/mbc.6.7.793
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- ↑ Stoler S, Keith KC, Curnick KE, Fitzgerald-Hayes M. A mutation in CSE4, an essential gene encoding a novel chromatin-associated protein in yeast, causes chromosome nondisjunction and cell cycle arrest at mitosis. Genes Dev. 1995 Mar 1;9(5):573-86. PMID:7698647
- ↑ Meluh PB, Yang P, Glowczewski L, Koshland D, Smith MM. Cse4p is a component of the core centromere of Saccharomyces cerevisiae. Cell. 1998 Sep 4;94(5):607-13. PMID:9741625
- ↑ Baker RE, Harris K, Zhang K. Mutations synthetically lethal with cep1 target S. cerevisiae kinetochore components. Genetics. 1998 May;149(1):73-85. PMID:9584087
- ↑ Keith KC, Baker RE, Chen Y, Harris K, Stoler S, Fitzgerald-Hayes M. Analysis of primary structural determinants that distinguish the centromere-specific function of histone variant Cse4p from histone H3. Mol Cell Biol. 1999 Sep;19(9):6130-9. PMID:10454560
- ↑ Keith KC, Fitzgerald-Hayes M. CSE4 genetically interacts with the Saccharomyces cerevisiae centromere DNA elements CDE I and CDE II but not CDE III. Implications for the path of the centromere dna around a cse4p variant nucleosome. Genetics. 2000 Nov;156(3):973-81. PMID:11063678
- ↑ Glowczewski L, Yang P, Kalashnikova T, Santisteban MS, Smith MM. Histone-histone interactions and centromere function. Mol Cell Biol. 2000 Aug;20(15):5700-11. PMID:10891506
- ↑ Tanaka T, Cosma MP, Wirth K, Nasmyth K. Identification of cohesin association sites at centromeres and along chromosome arms. Cell. 1999 Sep 17;98(6):847-58. PMID:10499801
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- ↑ Collins KA, Castillo AR, Tatsutani SY, Biggins S. De novo kinetochore assembly requires the centromeric histone H3 variant. Mol Biol Cell. 2005 Dec;16(12):5649-60. Epub 2005 Oct 5. PMID:16207811 doi:http://dx.doi.org/10.1091/mbc.E05-08-0771
- ↑ Hajra S, Ghosh SK, Jayaram M. The centromere-specific histone variant Cse4p (CENP-A) is essential for functional chromatin architecture at the yeast 2-microm circle partitioning locus and promotes equal plasmid segregation. J Cell Biol. 2006 Sep 11;174(6):779-90. PMID:16966420 doi:http://dx.doi.org/jcb.200603042
- ↑ Schleiffer A, Maier M, Litos G, Lampert F, Hornung P, Mechtler K, Westermann S. CENP-T proteins are conserved centromere receptors of the Ndc80 complex. Nat Cell Biol. 2012 May 6;14(6):604-13. doi: 10.1038/ncb2493. PMID:22561346 doi:http://dx.doi.org/10.1038/ncb2493
- ↑ Poddar A, Roy N, Sinha P. MCM21 and MCM22, two novel genes of the yeast Saccharomyces cerevisiae are required for chromosome transmission. Mol Microbiol. 1999 Jan;31(1):349-60. PMID:9987135
- ↑ Sanyal K, Ghosh SK, Sinha P. The MCM16 gene of the yeast Saccharomyces cerevisiae is required for chromosome segregation. Mol Gen Genet. 1998 Nov;260(2-3):242-50. PMID:9862478
- ↑ Poddar A, Roy N, Sinha P. MCM21 and MCM22, two novel genes of the yeast Saccharomyces cerevisiae are required for chromosome transmission. Mol Microbiol. 1999 Jan;31(1):349-60. PMID:9987135
- ↑ De Wulf P, McAinsh AD, Sorger PK. Hierarchical assembly of the budding yeast kinetochore from multiple subcomplexes. Genes Dev. 2003 Dec 1;17(23):2902-21. Epub 2003 Nov 21. PMID:14633972 doi:http://dx.doi.org/10.1101/gad.1144403
- ↑ Schleiffer A, Maier M, Litos G, Lampert F, Hornung P, Mechtler K, Westermann S. CENP-T proteins are conserved centromere receptors of the Ndc80 complex. Nat Cell Biol. 2012 May 6;14(6):604-13. doi: 10.1038/ncb2493. PMID:22561346 doi:http://dx.doi.org/10.1038/ncb2493
- ↑ Martini EM, Keeney S, Osley MA. A role for histone H2B during repair of UV-induced DNA damage in Saccharomyces cerevisiae. Genetics. 2002 Apr;160(4):1375-87. PMID:11973294
- ↑ Briggs SD, Xiao T, Sun ZW, Caldwell JA, Shabanowitz J, Hunt DF, Allis CD, Strahl BD. Gene silencing: trans-histone regulatory pathway in chromatin. Nature. 2002 Aug 1;418(6897):498. Epub 2002 Jul 14. PMID:12152067 doi:10.1038/nature00970
- ↑ Kao CF, Hillyer C, Tsukuda T, Henry K, Berger S, Osley MA. Rad6 plays a role in transcriptional activation through ubiquitylation of histone H2B. Genes Dev. 2004 Jan 15;18(2):184-95. PMID:14752010 doi:10.1101/gad.1149604
- ↑ Yamashita K, Shinohara M, Shinohara A. Rad6-Bre1-mediated histone H2B ubiquitylation modulates the formation of double-strand breaks during meiosis. Proc Natl Acad Sci U S A. 2004 Aug 3;101(31):11380-5. Epub 2004 Jul 27. PMID:15280549 doi:10.1073/pnas.0400078101
- ↑ Ahn SH, Cheung WL, Hsu JY, Diaz RL, Smith MM, Allis CD. Sterile 20 kinase phosphorylates histone H2B at serine 10 during hydrogen peroxide-induced apoptosis in S. cerevisiae. Cell. 2005 Jan 14;120(1):25-36. PMID:15652479 doi:S009286740401092X
- ↑ Ahn SH, Henderson KA, Keeney S, Allis CD. H2B (Ser10) phosphorylation is induced during apoptosis and meiosis in S. cerevisiae. Cell Cycle. 2005 Jun;4(6):780-3. Epub 2005 Jun 14. PMID:15970663
- ↑ Giannattasio M, Lazzaro F, Plevani P, Muzi-Falconi M. The DNA damage checkpoint response requires histone H2B ubiquitination by Rad6-Bre1 and H3 methylation by Dot1. J Biol Chem. 2005 Mar 18;280(11):9879-86. Epub 2005 Jan 4. PMID:15632126 doi:M414453200
- ↑ Xiao T, Kao CF, Krogan NJ, Sun ZW, Greenblatt JF, Osley MA, Strahl BD. Histone H2B ubiquitylation is associated with elongating RNA polymerase II. Mol Cell Biol. 2005 Jan;25(2):637-51. PMID:15632065 doi:25/2/637
- ↑ Nathan D, Ingvarsdottir K, Sterner DE, Bylebyl GR, Dokmanovic M, Dorsey JA, Whelan KA, Krsmanovic M, Lane WS, Meluh PB, Johnson ES, Berger SL. Histone sumoylation is a negative regulator in Saccharomyces cerevisiae and shows dynamic interplay with positive-acting histone modifications. Genes Dev. 2006 Apr 15;20(8):966-76. Epub 2006 Apr 5. PMID:16598039 doi:gad.1404206
- ↑ Roy N, Poddar A, Lohia A, Sinha P. The mcm17 mutation of yeast shows a size-dependent segregational defect of a mini-chromosome. Curr Genet. 1997 Sep;32(3):182-9. PMID:9339342
- ↑ Cheeseman IM, Anderson S, Jwa M, Green EM, Kang J, Yates JR 3rd, Chan CS, Drubin DG, Barnes G. Phospho-regulation of kinetochore-microtubule attachments by the Aurora kinase Ipl1p. Cell. 2002 Oct 18;111(2):163-72. PMID:12408861
- ↑ Ortiz J, Stemmann O, Rank S, Lechner J. A putative protein complex consisting of Ctf19, Mcm21, and Okp1 represents a missing link in the budding yeast kinetochore. Genes Dev. 1999 May 1;13(9):1140-55. PMID:10323865
- ↑ De Wulf P, McAinsh AD, Sorger PK. Hierarchical assembly of the budding yeast kinetochore from multiple subcomplexes. Genes Dev. 2003 Dec 1;17(23):2902-21. Epub 2003 Nov 21. PMID:14633972 doi:http://dx.doi.org/10.1101/gad.1144403
- ↑ Yan K, Yang J, Zhang Z, McLaughlin SH, Chang L, Fasci D, Ehrenhofer-Murray AE, Heck AJR, Barford D. Structure of the inner kinetochore CCAN complex assembled onto a centromeric nucleosome. Nature. 2019 Oct 2. pii: 10.1038/s41586-019-1609-1. doi:, 10.1038/s41586-019-1609-1. PMID:31578520 doi:http://dx.doi.org/10.1038/s41586-019-1609-1
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