Affinage

CENPC

Centromere protein C · UniProt Q03188

Length
943 aa
Mass
106.8 kDa
Annotated
2026-04-28
100 papers in source corpus 45 papers cited in narrative 44 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CENP-C is the central scaffolding protein of the inner kinetochore, linking centromeric CENP-A chromatin to the outer kinetochore machinery and organizing the constitutive centromere-associated network (CCAN). It recognizes CENP-A nucleosomes through two conserved motifs that engage the CENP-A C-terminal tail hydrophobic region and the H2A/H2B acidic patch, allosterically reshaping and rigidifying CENP-A nucleosome structure to stabilize centromeric chromatin (PMID:23723239, PMID:25954010, PMID:26878239). Its N-terminal motif directly recruits the Mis12 complex — thereby bridging the KMN outer kinetochore network — while its PEST domain recruits the CENP-HIKM and CENP-TW subcomplexes, and its C-terminal Cupin domain mediates essential self-oligomerization for CCAN organization; these interactions are regulated by CDK1 phosphorylation (enhancing CENP-A binding in mitosis), Aurora B phosphorylation (modulating Mis12 interaction), and an auto-inhibitory mechanism relieved by CENP-A nucleosome engagement (PMID:21353556, PMID:26124289, PMID:37295434, PMID:31676716, PMID:29180432, PMID:32515113). CENP-C additionally recruits M18BP1/Mis18 complex to promote new CENP-A deposition, coupling kinetochore structure to epigenetic centromere maintenance (PMID:21911481, PMID:22540025).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1992 High

    Establishing CENP-C as a bona fide inner kinetochore plate component resolved the molecular identity of the inner centromere-microtubule interface.

    Evidence Immunoelectron microscopy with antibodies to cDNA-encoded fusion proteins in human cells

    PMID:1339310

    Open questions at the time
    • No functional data on what CENP-C does at the kinetochore
    • No binding partners identified
  2. 1994 High

    Antibody injection demonstrated that CENP-C is functionally required for kinetochore assembly and microtubule attachment, transforming it from a structural marker to a functional component.

    Evidence Anti-CENP-C antibody microinjection causing metaphase arrest, reduced kinetochore diameter, and failure of microtubule binding

    PMID:8175879

    Open questions at the time
    • Mechanism of kinetochore assembly role unknown
    • No molecular partners identified
  3. 1995 High

    CENP-C presence exclusively at active (not inactive) centromeres of dicentric chromosomes, combined with yeast Mif2 genetic interactions with CBF proteins, established CENP-C as an evolutionarily conserved component specifically of functional centromeres.

    Evidence Immunofluorescence/FISH on dicentric chromosomes; genetic epistasis of mif2 with centromere genes in S. cerevisiae

    PMID:7579695 PMID:8634687

    Open questions at the time
    • No direct biochemical interaction with centromeric chromatin demonstrated
    • Mechanism of centromere specificity unknown
  4. 1997 Medium

    Domain-mapping studies revealed CENP-C as a modular protein with separable DNA-binding, centromere-targeting, and C-terminal dimerization functions, providing the first architectural framework.

    Evidence South-Western blotting, chemical cross-linking, gel filtration, and in vivo GFP-truncation analysis

    PMID:7883764 PMID:8668174 PMID:9146917

    Open questions at the time
    • DNA binding shown only in vitro with non-centromeric substrates
    • Dimerization function not linked to in vivo kinetochore role
  5. 1999 High

    Conditional CENP-C knockout in DT40 cells proved CENP-C is essential for maintaining the entire centromere protein complex, not just one downstream effector, establishing its role as a central scaffold.

    Evidence Conditional gene disruption in chicken DT40 cells with immunofluorescence analysis of centromere complex integrity

    PMID:10428958

    Open questions at the time
    • Identity of the downstream centromere proteins dependent on CENP-C not fully catalogued
    • No direct protein-protein interactions mapped
  6. 2001 High

    Epistasis experiments in vertebrate and worm systems placed CENP-C downstream of CENP-A/CENP-H and upstream of outer kinetochore proteins, defining its position in the assembly hierarchy.

    Evidence Conditional CENP-H knockout in DT40 and HCP-4 RNAi in C. elegans with localization epistasis readouts

    PMID:11402064 PMID:11500386

    Open questions at the time
    • Direct physical basis for CENP-A → CENP-C → outer kinetochore connections not established
    • Whether hierarchy is identical across organisms unclear
  7. 2007 High

    CENP-C depletion was shown to reduce Mis12 complex at centromeres and impair the Mad2 checkpoint pathway, identifying Mis12 as a key downstream effector and linking CENP-C to checkpoint signaling.

    Evidence Conditional CENP-C knockout in DT40 with live imaging, nocodazole checkpoint assay, and immunofluorescence for Mis12

    PMID:17392512

    Open questions at the time
    • Whether CENP-C contacts Mis12 complex directly or indirectly unknown
    • Checkpoint defect could be indirect consequence of reduced kinetochore
  8. 2009 High

    Reconstitution in Xenopus egg extracts and fission yeast identified specific CENP-C domains that directly recruit Mis12/MIND complex and CENP-L, establishing CENP-C as a multi-arm scaffold with separable effector-binding surfaces.

    Evidence Xenopus egg extract immunodepletion/complementation with domain mutants; yeast two-hybrid and co-IP of Cnp3-Fta1 in S. pombe

    PMID:19641019 PMID:19758558

    Open questions at the time
    • Atomic basis of CENP-C–Mis12 interaction not yet resolved
    • CENP-HIKM recruitment mechanism not addressed
  9. 2011 High

    Direct high-affinity binding between a conserved CENP-C N-terminal motif and the Mis12 complex was demonstrated, providing the molecular link between inner and outer kinetochore; separately, CENP-C was shown to recruit M18BP1/Mis18 for CENP-A loading, connecting kinetochore architecture to centromere propagation.

    Evidence In vitro direct binding and dominant-negative expression in human/Drosophila cells for Mis12; RNAi and direct binding assays for M18BP1 in human/Xenopus systems

    PMID:21353555 PMID:21353556 PMID:21911481

    Open questions at the time
    • Structural basis of CENP-C–Mis12 interface not resolved
    • How CENP-C coordinates Mis12 recruitment and M18BP1 recruitment temporally unclear
  10. 2013 High

    Crystal structures revealed how CENP-C recognizes CENP-A nucleosomes: the CENP-C motif docks onto the CENP-A tail hydrophobic region and the H2A/H2B acidic patch, providing the first atomic-resolution view of centromere-specific chromatin recognition.

    Evidence X-ray crystallography and NMR of CENP-C motif bound to CENP-A nucleosome, with mutagenesis validation

    PMID:23723239

    Open questions at the time
    • How full-length CENP-C engages the nucleosome in situ unknown
    • Role of the second CENP-A-binding region (central domain) not structurally resolved
  11. 2015 High

    Biophysical reconstitution demonstrated that CENP-C binding allosterically reshapes CENP-A nucleosomes — rigidifying both surface and internal structure and modulating DNA wrapping — revealing CENP-C as an active chromatin remodeler rather than a passive reader; separately, the PEST domain was identified as the CENP-HIKM recruitment site.

    Evidence Hydrogen-deuterium exchange, FRET, and CENP-C depletion for nucleosome reshaping; biochemical reconstitution and mutagenesis for PEST–CENP-HIKM interaction

    PMID:25660545 PMID:25954010 PMID:26124289

    Open questions at the time
    • Structural basis of CENP-C–CENP-HIKM interaction at atomic resolution unknown
    • Whether reshaping occurs on native centromeric chromatin in vivo not shown
  12. 2016 High

    Crystal structures of the Mis12 complex bound to a CENP-C fragment revealed the structural basis of the inner-to-outer kinetochore bridge and showed Aurora B phosphorylation regulates this interface, providing a mechanism for error correction.

    Evidence X-ray crystallography of human MIS12–CENP-C complex, in vitro kinase assay

    PMID:27881301

    Open questions at the time
    • How Aurora B accesses CENP-C at the kinetochore in vivo not established
    • Quantitative regulation during error correction not measured
  13. 2019 High

    CDK1 phosphorylation of the CENP-C C-terminal region was shown to enhance CENP-A nucleosome binding in mitosis, providing a cell-cycle switch that strengthens CENP-C kinetochore localization specifically when needed; concurrently, cryo-EM revealed the CENP-C central region destabilizes H2A C-terminal tail and rigidifies H4 N-tail to favor H4K20me1.

    Evidence In vitro kinase assay and phospho-mutant analysis for CDK1 regulation; cryo-EM and NMR for structural mechanism

    PMID:31475439 PMID:31676716

    Open questions at the time
    • Whether CDK1 and Aurora B phosphorylation are coordinated on the same CENP-C molecule unknown
    • Functional significance of H4K20me1 promotion at centromeres not directly tested
  14. 2020 High

    Demonstration that Mif2/CENP-C is auto-inhibited for Mis12 binding until relieved by CENP-A nucleosome engagement provided a conformational switch ensuring outer kinetochore assembly occurs only at centromeric chromatin.

    Evidence In vitro reconstitution with purified yeast components; bypass mutant causing ectopic Mtw1 localization and segregation defects

    PMID:32515113

    Open questions at the time
    • Whether auto-inhibition operates in vertebrate CENP-C not demonstrated
    • Structural basis of the conformational change not resolved
  15. 2023 High

    Crystal structures of the CENP-C Cupin domain showed that self-oligomerization is essential for CCAN assembly and centromeric chromatin organization, completing the picture of CENP-C as a multi-domain scaffold whose dimerization underlies higher-order centromere architecture.

    Evidence Crystal structures of chicken and human Cupin domains, oligomerization assays, complementation of CENP-C mutants in cells

    PMID:37295434

    Open questions at the time
    • How Cupin-mediated oligomerization interfaces with CENP-A nucleosome arrays in situ unknown
    • Stoichiometry of CENP-C oligomers at native centromeres not determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • A full structural model of CENP-C engaged with a CENP-A nucleosome and simultaneously bound to Mis12, CENP-HIKM, and M18BP1 — capturing the integrated hub architecture — remains unresolved.
  • No structure of full-length CENP-C in complex with its multiple binding partners
  • Whether the auto-inhibition mechanism discovered in yeast operates in human CENP-C is untested
  • How lncRNA and centromeric transcripts contribute to CENP-C recruitment in vivo under physiological conditions is incompletely resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 5 GO:0005198 structural molecule activity 5 GO:0042393 histone binding 4 GO:0003723 RNA binding 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005694 chromosome 6 GO:0005634 nucleus 3
Pathway
R-HSA-1640170 Cell Cycle 8 R-HSA-4839726 Chromatin organization 5
Partners
CENPACENPHCENPICENPKDNMT3BDSN1M18BP1MIS12
Complex memberships
CCAN (constitutive centromere-associated network)CENP-A nucleosome complex

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 CENP-C is a component of the human inner kinetochore plate, as established by immunoelectron microscopy using antibodies raised to cDNA-encoded fusion proteins. Immunoelectron microscopy, immunoblotting, indirect immunofluorescence Cell High 1339310
1994 CENP-C is required for maintaining proper kinetochore size and for a timely transition to anaphase; nuclear microinjection of anti-CENP-C antibodies during interphase causes metaphase arrest, reduces CENP-C at centromeres, and results in kinetochores of reduced diameter that fail to bind microtubules. Nuclear microinjection of antibodies, indirect immunofluorescence, electron microscopy The Journal of cell biology High 8175879
1994 CENP-C is a DNA-binding protein; recombinant human CENP-C binds DNA in vitro through an internal ~101-amino acid domain with no homology to known DNA-binding proteins. South-Western blotting, truncation analysis, recombinant protein expression Journal of biochemistry Medium 7883764
1995 CENP-C is selectively present at active centromeres but absent from inactive centromeres of dicentric chromosomes, establishing it as a necessary component of functional centromeres. Immunofluorescence with specific antibodies on dicentric chromosomes, simultaneous FISH Human molecular genetics High 7757082 8634687
1995 The yeast CENP-C ortholog Mif2 functions at the centromere and genetically interacts with CEP1/CBF1, NDC10/CBF2, and CEP3/CBF3B centromere protein genes; two regions of homology between Mif2 and CENP-C are identified, and temperature-sensitive mif2 mutations map within these conserved regions. Genetic epistasis, synthetic lethality screens, suppressor analysis Molecular biology of the cell High 7579695
1996 CENP-C contains an autonomous centromere-targeting domain in its central region that overlaps with its DNA-binding domain; mutations in the Mif2 homology domain impair kinetochore assembly. In vivo truncation/expression analysis of GFP-tagged constructs, in vitro DNA-binding assays Molecular and cellular biology High 8668174
1996 CENP-C interacts in vitro and in vivo with nucleolar transcription factors UBF1 and UBF2 (NOR-90) through the carboxyl-terminal third of CENP-C; a subset of CENP-C and UBF co-localizes at nucleoli in interphase HeLa cells. Affinity chromatography, microsequencing, co-immunofluorescence The Journal of biological chemistry Medium 8702533
1997 Human CENP-C has three functional domains: a putative N-terminal oligomerization domain, an internal DNA-binding domain (with 'core' and 'stabilizing' elements), and a C-terminal dimerization domain; the C-terminus forms dimers in the native state. In vitro DNA-binding assay (South-Western), chemical cross-linking, gel filtration Chromosome research Medium 9146917
1998 CENP-C interacts with HDaxx (human Daxx) in an interphase-specific manner; the interaction is mediated by the N-terminal 315 amino acids of CENP-C and the C-terminal 104 amino acids of HDaxx, with co-localization at discrete nuclear spots in interphase. Yeast interaction trap, co-immunofluorescence Journal of cell science Medium 9645950
1999 CENP-C is necessary for centromere complex assembly; loss of CENP-C from centromeres in chicken DT40 cells disassembles the centromere protein complex and blocks cells at the metaphase-anaphase junction. Conditional gene disruption in DT40 cells, immunofluorescence The EMBO journal High 10428958
1999 HSV-1 immediate-early protein Vmw110 (ICP0) causes proteasome-dependent loss of CENP-C from centromeres via its RING finger domain, resulting in substantial ultrastructural changes in the kinetochore and mitotic arrest or aberrant cytokinesis. Viral infection assays, immunofluorescence, electron microscopy, proteasome inhibitor treatment The EMBO journal High 10075924
2001 CENP-H is required for centromere targeting of CENP-C but not CENP-A in vertebrate cells, placing CENP-H upstream of CENP-C in a hierarchical centromere assembly pathway. Conditional knockout in DT40 cells, immunocytochemistry The EMBO journal High 11500386
2001 C. elegans HCP-4 (CENP-C ortholog) is required for sister centromere resolution and kinetochore formation; HCP-4 localization depends on the centromeric histone HCP-3, and HCP-4 is in turn required for localization of the CENP-F-like protein HCP-1, establishing an ordered assembly pathway. RNAi, immunofluorescence, localization epistasis The Journal of cell biology High 11402064
2001 Temperature-sensitive CENP-C mutants in DT40 cells cause metaphase delay and chromosome missegregation; SUMO-1 overexpression suppresses the temperature-sensitive phenotype, implicating SUMO-1 in centromere function. Gene targeting in DT40 cells, cDNA library suppressor screen, temperature-shift experiments Nucleic acids research Medium 11557811
2002 CENP-C binds alpha-satellite DNA selectively in vivo; the region between amino acids 410 and 537 is required for in vivo DNA binding, and CENP-C and CENP-B associate with the same alpha-satellite array types but in distinct non-overlapping centromere domains. Chromatin immunoprecipitation (ChIP), truncation mutant analysis, immunoelectron microscopy Journal of cell science High 12006616
2003 CENP-B interacts directly with CENP-C; the CENP-C domains required overlap with three Mif2 homologous regions also involved in centromere assembly; overproduction of truncated CENP-B lacking CENP-C interaction domains causes abnormal CENP-C domain duplication and cell cycle delay. Yeast two-hybrid, domain mapping by truncation, cellular overexpression assay The Journal of biological chemistry Medium 14612452
2004 Human CENP-C is SUMOylated in vitro by SUMO-1 and SUMO-2 at multiple lysine residues, including sites outside the canonical consensus sumoylation motif; the consensus sumoylation motif of CENP-C partially overlaps its DNA-binding and centromere localization domain. In vitro sumoylation reconstitution, tandem mass spectrometry identification of isopeptides The Journal of biological chemistry Medium 15272016
2007 CENP-C inactivation in chicken DT40 cells causes mitotic delay, chromosome missegregation, and impairs the Mad2 spindle checkpoint pathway; CENP-C depletion significantly reduces Mis12 complex proteins at centromeres, placing CENP-C upstream of the Mis12 complex. Conditional knockout (tetracycline-inducible) in DT40 cells, live imaging, immunofluorescence, nocodazole checkpoint assay Molecular biology of the cell High 17392512
2007 During death receptor-induced apoptosis, activated caspase-7 cleaves CENP-C (and INCENP), leading to mislocalization of CENP-C and displacement of Aurora B kinase from centromeres; expression of non-cleavable CENP-C prevents passenger complex mislocalization. Caspase inhibitor treatment, site-directed mutagenesis of cleavage sites, immunofluorescence Molecular biology of the cell Medium 17287400
2009 The N-terminus of CENP-C promotes kinetochore assembly by ensuring proper targeting of the Mis12/MIND complex and CENP-K; CENP-C mutants that localize to centromeres but fail to support kinetochore assembly were identified using Xenopus egg extract immunodepletion/complementation. Xenopus egg extract immunodepletion, in vitro translation complementation, immunofluorescence Molecular biology of the cell High 19641019
2009 DNMT3B interacts with CENP-C (identified by yeast two-hybrid and confirmed by co-immunoprecipitation); CENP-C recruits DNMT3B and DNA methylation to centromeric and pericentromeric repeats, and both proteins regulate histone marks in these regions. Yeast two-hybrid, co-immunoprecipitation, siRNA knockdown, bisulfite sequencing, ChIP Human molecular genetics High 19482874
2009 The C-terminal Mif2p homology domain III of CENP-C mediates homo-dimerization and homo-oligomerization, and mediates interactions with CENP-A and histone H3; domain II contacts alpha-satellite DNA and targets the centromere. Co-immunoprecipitation, bimolecular fluorescence complementation, ChIP, immunofluorescence PloS one Medium 19503796
2009 Fission yeast CENP-C (Cnp3) serves as a scaffold for kinetochore effectors: Fta1/CENP-L binds directly to Cnp3, and ectopic Fta1 suppresses cnp3Δ mitotic defects; in meiosis, Cnp3 associates with and recruits the meiosis-specific protein Moa1 for mono-orientation of kinetochores. Genetic epistasis, yeast two-hybrid, co-immunoprecipitation, ectopic localization rescue Developmental cell High 19758558
2010 CENP-C DNA binding is stabilized by single-stranded RNA; a localized 122-amino acid domain confers DNA binding, and long single-stranded RNAs matching centromeric RNAs in size strongly promote CENP-C binding to DNA in vitro; removal of the binding module causes partial delocalization in vivo. In vitro DNA-binding assays with RNA titration, domain deletion/substitution, in vivo localization PLoS genetics Medium 20140237
2011 The N-terminal region of CENP-C contains a conserved motif that binds directly and with high affinity to the Mis12 complex, providing the key link between inner and outer kinetochore; expression of the isolated N-terminal Mis12-binding motif prevents outer kinetochore assembly and impairs the spindle assembly checkpoint. Direct binding assay, in vitro pulldown, dominant-negative expression in HeLa cells, immunofluorescence, checkpoint assay Current biology : CB High 21353556
2011 Drosophila CENP-C N-terminal region binds all KMN network components (Mis12 complex, Ndc80 complex, Spc105/KNL1); the Mis12 complex component Nnf1 interacts directly with CENP-C in vitro; targeting CENP-C N-terminus to centrosomes recruits KMN proteins at the expense of centromeres. In vitro pulldown, ectopic targeting assay (fusion to Plk4 centrosome domain), immunofluorescence Current biology : CB High 21353555
2011 CENP-C recruits M18BP1 (of the Mis18 complex) to centromeres; depletion of CENP-C prevents M18BP1 targeting to metaphase centromeres and inhibits CENP-A chromatin assembly; M18BP1 directly binds CENP-C through conserved CENP-C domains. RNAi depletion, direct binding assay, co-immunoprecipitation, immunofluorescence The Journal of cell biology High 21911481
2012 M18BP1 interacts directly with the C-terminus of CENP-C via a central SANT domain-containing region; knockdown of CENP-C reduces M18BP1 association and CENP-A levels at centromeres. Co-immunoprecipitation interaction screen, domain mapping, siRNA knockdown, immunofluorescence Nucleus (Austin, Tex.) High 22540025
2013 CENP-C binds a hydrophobic region in the CENP-A C-terminal tail and docks onto the acidic patch of H2A/H2B on the nucleosome; the conserved CENP-C motif uses the same mechanism for CENP-A nucleosome recognition, revealing a conserved mechanism for centromere protein recruitment. Crystal structure determination, NMR, biochemical binding assays, mutagenesis Science (New York, N.Y.) High 23723239
2015 CENP-C reshapes and rigidifies CENP-A nucleosomes using purified components: it changes the octameric histone core structure, rigidifies both surface and internal nucleosome structure, and modulates terminal DNA wrapping to match native CENP-A nucleosomes; CENP-C depletion leads to rapid removal of CENP-A from centromeres. In vitro reconstitution with purified components, hydrogen-deuterium exchange, FRET, CENP-C depletion Science (New York, N.Y.) High 25954010
2015 The PEST domain in the N-terminal half of CENP-C interacts directly with the CENP-HIKM subcomplex; this interaction is required for kinetochore localization of CENP-HIKM and subsequently CENP-TW, establishing CENP-C as a blueprint for CCAN assembly. Biochemical reconstitution, co-immunoprecipitation, structure-guided mutagenesis, cellular kinetochore localization assay The Journal of cell biology High 26124289
2015 CENP-C and CENP-T recruit the KMN network through distinct pathways: CENP-C recruits Ndc80 complex through KNL1 and Mis12 complex interactions, while CENP-T directly interacts with Ndc80; Aurora B kinase promotes KMN network recruitment to CENP-C whereas CDK regulates recruitment to CENP-T. Ectopic targeting to lac operator locus, domain mapping, kinase inhibitor treatment, immunofluorescence Current biology : CB High 25660545
2015 CENP-C depletion in Xenopus egg extracts results in reduced CENP-T at centromeres and decreased recruitment of Ndc80 and Mis12, supporting two parallel pathways (CENP-C and CENP-T/W) for kinetochore assembly; CENP-C but not CENP-T/W participates in CENP-A deposition. Xenopus egg extract immunodepletion, immunofluorescence, cell-free reconstitution Nucleus (Austin, Tex.) Medium 25569378
2016 Crystal structures of human MIS12 complex bound to a CENP-C fragment reveal the structural basis for the CENP-C–Mis12 interaction; Aurora B kinase phosphorylation regulates this interaction. X-ray crystallography, in vitro binding assay, kinase phosphorylation assay Cell High 27881301
2016 CENP-C reshapes CENP-A nucleosome structure mainly through sliding of DNA gyres back toward canonical H3 nucleosome positions, as demonstrated by single-molecule FRET using recombinant human histones. Single-molecule FRET, recombinant nucleosome reconstitution Nature structural & molecular biology High 26878239
2017 Active centromere alpha-satellite transcripts are complexed with CENP-A and CENP-C; depletion of array-specific RNAs reduces CENP-A and CENP-C at the targeted centromere via faulty CENP-A loading. RNA immunoprecipitation, RNA interference, immunofluorescence, ChIP Developmental cell Medium 28787590
2017 CENP-C motif and CENP-C central region both bind exclusively to CENP-A nucleosomes; in yeast, Mif2/CENP-C contacts one side of the nucleosome dyad engaging both the Cse4/CENP-A histone-fold domain and AT-rich centromere DNA through a contiguous DNA- and histone-binding domain (DHBD) harboring the CENP-C motif, an AT hook, and RK clusters. Biochemical binding assays, structural analysis, ChIP, mutagenesis Genes & development High 29074736
2017 Aurora B phosphorylation of CENP-C (Thr28 in S. pombe Cnp3) impairs the interaction between CENP-C and the Mis12 complex; phosphorylation-mimicking CENP-C mutant results in defective chromosome segregation due to improper kinetochore assembly. Crystal structure determination, in vitro kinase assay, co-immunoprecipitation, mutant expression assay Proceedings of the National Academy of Sciences of the United States of America High 29180432
2019 CDK1-mediated phosphorylation of the CENP-C C-terminal region facilitates CENP-C binding to CENP-A nucleosomes in vitro and in vivo; enhanced CENP-A–CENP-C interaction promotes CENP-C kinetochore localization during mitosis. In vitro kinase assay, co-immunoprecipitation, phospho-mutant analysis, conditional depletion The Journal of cell biology High 31676716
2019 CENP-C central region (CENP-CCR) binds CENP-A nucleosomes with high affinity through an extended hydrophobic area involving CENP-A V532 and V533; CENP-C binding causes two conformational changes: further exacerbation of loose DNA wrapping through destabilization of the H2A C-terminal tail, and rigidification of the H4 N-terminal tail favoring H4K20 monomethylation. Cryo-EM, NMR, in vitro binding assay, mutagenesis EMBO reports High 31475439
2020 Mif2/CENP-C is auto-inhibited in its ability to bind the Mtw1 (Mis12) complex; addition of Cse4/CENP-A nucleosomes overcomes this auto-inhibition. A Mif2 mutant bypassing Cse4 requirement for Mtw1 binding causes mis-localization of the Mtw1 complex and chromosome segregation defects in vivo. Biochemical reconstitution, in vitro binding assay, genetic mutant analysis The EMBO journal High 32515113
2022 A lncRNA (CCTT) recruits CENP-C to centromeres via RNA-DNA triplex formation and direct RNA-protein interaction with CENP-C; loss of CCTT reduces CENP-C at centromeres and triggers extensive mitotic errors and aneuploidy. RNA-DNA triplex assay, RNA immunoprecipitation, CENP-C co-immunoprecipitation, siRNA knockdown, live imaging Molecular cell Medium 36332605
2023 CENP-C self-oligomerization via its Cupin domain is essential for CCAN assembly, centromeric chromatin organization, and centromeric localization of CCAN components; structural and biochemical analyses reveal distinct dimerization modes of the Cupin domain in chicken and human CENP-C. Crystal structure, biochemical oligomerization assay, CENP-C mutant complementation in cells, immunofluorescence Molecular cell High 37295434
2023 Multi-site phosphorylation of yeast Mif2/CENP-C PEST region enhances inner kinetochore assembly; elimination of phosphorylation sites progressively impairs cellular fitness and is lethal in cells lacking non-essential inner kinetochore factors. Phospho-mutant genetic analysis, epistasis with inner kinetochore deletion mutants Current biology : CB Medium 36736323

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Evidence that the MIF2 gene of Saccharomyces cerevisiae encodes a centromere protein with homology to the mammalian centromere protein CENP-C. Molecular biology of the cell 368 7579695
1992 CENP-C, an autoantigen in scleroderma, is a component of the human inner kinetochore plate. Cell 325 1339310
2007 Incorporation of Drosophila CID/CENP-A and CENP-C into centromeres during early embryonic anaphase. Current biology : CB 299 17222555
1989 Visualization of centromere proteins CENP-B and CENP-C on a stable dicentric chromosome in cytological spreads. Chromosoma 282 2475307
2013 A conserved mechanism for centromeric nucleosome recognition by centromere protein CENP-C. Science (New York, N.Y.) 274 23723239
2011 CENP-C is a structural platform for kinetochore assembly. Current biology : CB 223 21353555
2011 Direct binding of Cenp-C to the Mis12 complex joins the inner and outer kinetochore. Current biology : CB 219 21353556
1999 Specific destruction of kinetochore protein CENP-C and disruption of cell division by herpes simplex virus immediate-early protein Vmw110. The EMBO journal 204 10075924
1995 Identification of centromeric antigens in dicentric Robertsonian translocations: CENP-C and CENP-E are necessary components of functional centromeres. Human molecular genetics 195 8634687
2011 CENP-C recruits M18BP1 to centromeres to promote CENP-A chromatin assembly. The Journal of cell biology 187 21911481
2015 Chromosomes. CENP-C reshapes and stabilizes CENP-A nucleosomes at the centromere. Science (New York, N.Y.) 181 25954010
1994 CENP-C is required for maintaining proper kinetochore size and for a timely transition to anaphase. The Journal of cell biology 175 8175879
2017 Human Centromeres Produce Chromosome-Specific and Array-Specific Alpha Satellite Transcripts that Are Complexed with CENP-A and CENP-C. Developmental cell 150 28787590
2012 D-dopachrome tautomerase (D-DT or MIF-2): doubling the MIF cytokine family. Cytokine 148 22507380
2001 CENP-H, a constitutive centromere component, is required for centromere targeting of CENP-C in vertebrate cells. The EMBO journal 145 11500386
2015 CENP-C is a blueprint for constitutive centromere-associated network assembly within human kinetochores. The Journal of cell biology 138 26124289
2016 Structure of the MIS12 Complex and Molecular Basis of Its Interaction with CENP-C at Human Kinetochores. Cell 131 27881301
2015 Distinct organization and regulation of the outer kinetochore KMN network downstream of CENP-C and CENP-T. Current biology : CB 115 25660545
2009 DNMT3B interacts with constitutive centromere protein CENP-C to modulate DNA methylation and the histone code at centromeric regions. Human molecular genetics 115 19482874
2012 CENP-C facilitates the recruitment of M18BP1 to centromeric chromatin. Nucleus (Austin, Tex.) 111 22540025
2009 Dissection of CENP-C-directed centromere and kinetochore assembly. Molecular biology of the cell 108 19641019
1998 Interphase-specific association of intrinsic centromere protein CENP-C with HDaxx, a death domain-binding protein implicated in Fas-mediated cell death. Journal of cell science 108 9645950
2007 CENP-C is involved in chromosome segregation, mitotic checkpoint function, and kinetochore assembly. Molecular biology of the cell 107 17392512
1996 Identification of overlapping DNA-binding and centromere-targeting domains in the human kinetochore protein CENP-C. Molecular and cellular biology 106 8668174
2010 DNA binding of centromere protein C (CENPC) is stabilized by single-stranded RNA. PLoS genetics 105 20140237
1993 MIF2 is required for mitotic spindle integrity during anaphase spindle elongation in Saccharomyces cerevisiae. The Journal of cell biology 101 8408221
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