Affinage

CENPC

Centromere protein C · UniProt Q03188

Length
943 aa
Mass
106.8 kDa
Annotated
2026-06-09
100 papers in source corpus 58 papers cited in narrative 58 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CENP-C is a conserved inner kinetochore scaffold that bridges centromeric chromatin to the outer kinetochore machinery and is essential for accurate chromosome segregation (PMID:1339310, PMID:9361037, PMID:10428958). It binds the CENP-A nucleosome directly, recognizing a hydrophobic region of the CENP-A tail and docking onto the H2A/H2B acidic patch through both its central region and the conserved CENP-C motif (PMID:23723239, PMID:31475439); this engagement reshapes the nucleosome by rigidifying the histone core and driving lateral DNA gyre sliding toward canonical positioning (PMID:25954010, PMID:26878239). CENP-C also contacts centromeric AT-rich/alpha-satellite DNA through internal DNA-binding/centromere-targeting domains, integrating histone and DNA recognition into contiguous binding modules (PMID:7883764, PMID:12006616, PMID:29074736). From this chromatin platform, the conserved N-terminal motif of CENP-C binds the Mis12 complex with high affinity to nucleate assembly of the full KMN network and outer kinetochore (PMID:19641019, PMID:21353556), while its PEST region recruits the CENP-HIKM subcomplex, establishing CENP-C as a blueprint for assembly of the broader CCAN (PMID:26124289). C-terminal Cupin-domain oligomerization and dimerization organize centromeric chromatin architecture and are required for CCAN localization (PMID:37295434, PMID:40997799). CENP-C additionally sustains the centromeric epigenetic state by recruiting the M18BP1/Mis18 complex to drive new CENP-A loading (PMID:21911481, PMID:22540025) and by recruiting DNMT3B to direct centromeric DNA methylation, with its loss increasing missegregation and centromeric repeat transcription (PMID:19482874). These activities are gated by mitotic kinases: CDK1 phosphorylation of the C-terminal region enhances CENP-A binding, whereas Aurora B phosphorylation of the N-terminal region modulates the Mis12 interaction for error correction, forming a positive regulatory loop that reinforces biorientation (PMID:27881301, PMID:29180432, PMID:31676716, PMID:39433344). Genetic and biochemical conservation from yeast Mif2 through worm, fly, and plant orthologs underlies roles in kinetochore assembly, the spindle assembly checkpoint, and meiotic functions including mono-orientation and PLK-1 recruitment (PMID:7579695, PMID:17392512, PMID:19758558, PMID:37067150).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1992 High

    Established CENP-C as a physical constituent of the kinetochore, anchoring all subsequent mechanistic work at the inner kinetochore plate.

    Evidence Immunoelectron microscopy and immunofluorescence with anti-CENP-C antibodies on HeLa chromosomes; dicentric chromosome analysis showing presence only at active centromeres

    PMID:1339310 PMID:2475307 PMID:8634687

    Open questions at the time
    • Did not define molecular interactions or how CENP-C is targeted
    • No information on assembly hierarchy
  2. 1994 High

    Demonstrated CENP-C is functionally required for kinetochore integrity and mitotic progression, and is itself a DNA-binding protein, moving it from marker to functional component.

    Evidence Nuclear antibody microinjection causing metaphase arrest and reduced kinetochore size; Southwestern blotting of recombinant CENP-C against alphoid DNA

    PMID:7883764 PMID:8175879

    Open questions at the time
    • DNA binding shown in vitro only
    • Did not identify protein partners mediating function
  3. 1997 High

    Resolved CENP-C's modular architecture (oligomerization, DNA-binding, dimerization units) and proved it is necessary but not sufficient for centromere function via conditional loss/gain of function.

    Evidence Chemical crosslinking, gel filtration and Southwestern blotting of fragments; conditional gene disruption and overexpression in DT40 cells

    PMID:10428958 PMID:8668174 PMID:9146917 PMID:9361037

    Open questions at the time
    • Functional roles of individual domains not yet linked to specific partners
    • Assembly hierarchy with other CENPs undefined
  4. 2001 High

    Placed CENP-C within an ordered assembly pathway, defining CENP-A → CENP-H → CENP-C hierarchy and its dependence on upstream factors.

    Evidence Conditional knockouts in DT40 cells and RNAi in C. elegans with epistatic localization analysis

    PMID:11402064 PMID:11500386 PMID:7579695

    Open questions at the time
    • Direct binding mechanism to CENP-A not yet structurally defined
    • Outer kinetochore recruitment mechanism unknown
  5. 2002 High

    Linked CENP-C to the spindle assembly checkpoint and outer-kinetochore Mis12 recruitment, and mapped its in vivo alpha-satellite DNA binding to discrete domains.

    Evidence Conditional knockout with Mad2 and Mis12 readouts in DT40; ChIP and truncation mapping for in vivo DNA binding

    PMID:12006616 PMID:12490152 PMID:17392512

    Open questions at the time
    • Whether Mis12 recruitment is direct was not established here
    • Mechanism connecting CENP-C to checkpoint signaling unresolved
  6. 2009 High

    Identified the N-terminal domain of CENP-C as the direct recruiter of the Mis12/MIND complex and linked CENP-C to DNA methylation and CENP-A maintenance, broadening its role beyond structural scaffolding.

    Evidence Xenopus egg extract depletion-complementation with domain mutants; DNMT3B yeast two-hybrid, co-IP, bisulfite sequencing and ChIP; fission yeast scaffold and meiotic effector analysis

    PMID:19482874 PMID:19503796 PMID:19641019 PMID:19758558

    Open questions at the time
    • High-resolution structure of the N-terminal–Mis12 interface not yet resolved
    • Mechanism coupling CENP-C to DNMT3B recruitment in chromatin context incomplete
  7. 2011 High

    Established that a conserved N-terminal motif binds the Mis12 complex with high affinity to nucleate the entire KMN network, defining CENP-C as the inner-to-outer kinetochore bridge, and that it recruits M18BP1 to drive CENP-A assembly.

    Evidence Direct biochemical binding reconstitution and dominant-negative/ectopic targeting in HeLa and Drosophila cells; in vitro M18BP1 binding with siRNA-based CENP-A assembly readout

    PMID:21353555 PMID:21353556 PMID:21911481

    Open questions at the time
    • Structural basis of the Mis12 interaction not yet solved at this stage
    • Regulation of the recruitment by mitotic kinases not yet defined
  8. 2013 High

    Provided the structural mechanism of CENP-A nucleosome recognition — CENP-A tail engagement plus H2A/H2B acidic-patch docking — explaining how CENP-C reads the centromeric histone mark.

    Evidence Crystallography, NMR, mutagenesis and biochemical binding assays across species

    PMID:23723239

    Open questions at the time
    • Did not address how binding alters nucleosome dynamics
    • Did not resolve regulation of the interaction in mitosis
  9. 2015 High

    Showed CENP-C actively reshapes CENP-A nucleosome structure and serves as the assembly blueprint for the CCAN, linking chromatin reading to architectural organization.

    Evidence In vitro reconstitution with single-molecule FRET/FLIM and depletion in cells; biochemical reconstitution mapping the PEST–CENP-HIKM interaction; ectopic targeting separating CENP-C and CENP-T KMN recruitment

    PMID:25660545 PMID:25954010 PMID:26124289 PMID:39433344

    Open questions at the time
    • Quantitative contribution of nucleosome reshaping to centromere identity unresolved
    • Coordination between parallel CENP-C and CENP-T recruitment arms incomplete
  10. 2016 High

    Solved the MIS12C–CENP-C structure and defined gyre sliding as the mechanism of nucleosome reshaping, with Aurora B phosphorylation regulating the Mis12 interaction.

    Evidence X-ray crystallography of MIS12C–CENP-C, Aurora B kinase assays, and single-molecule FRET measuring DNA gyre sliding

    PMID:26878239 PMID:27881301

    Open questions at the time
    • In vivo dynamics of phospho-regulation across the cell cycle incompletely mapped
    • Functional consequence of gyre sliding for centromere inheritance not fully established
  11. 2017 High

    Defined CENP-C's combined DNA- and histone-binding module and revealed dependence on centromeric RNA, integrating nucleic acid and histone recognition.

    Evidence Biochemical binding and mutational analysis of the DHBD in yeast and human CENP-C; RNA-IP and RNA depletion affecting CENP-C levels; CO-FISH showing centromere integrity maintenance

    PMID:28167779 PMID:28787590 PMID:29074736

    Open questions at the time
    • Mechanism by which RNA stabilizes CENP-C–DNA binding in vivo incompletely defined
    • Role in repeat integrity mechanistically separate from segregation not fully dissected
  12. 2019 High

    Established kinase control of CENP-C: CDK1 phosphorylation of the C-terminus enhances CENP-A binding while Aurora B phosphorylation of the N-terminus tunes Mis12 binding, defining cell-cycle-coupled regulation of its bridging functions.

    Evidence In vitro CDK1 kinase assays, Phos-tag, co-IP and viability assays in chicken/human cells; Aurora B phosphorylation of S. pombe Cnp3 with phosphomimetic mutants; cryo-EM of CENP-A nucleosome with CENP-C central region

    PMID:29180432 PMID:31475439 PMID:31676716

    Open questions at the time
    • Temporal interplay between CDK1 and Aurora B inputs on the same protein unresolved
    • How phospho-states are reset across mitosis not defined
  13. 2023 High

    Defined C-terminal Cupin-domain oligomerization as essential for centromeric chromatin organization and CCAN recruitment, and revealed auto-inhibition relieved by CENP-A binding.

    Evidence Crystal structure of the Cupin domain with biochemical oligomerization assays and mutagenesis in chicken cells; in vitro auto-inhibition reconstitution with yeast genetics; C. elegans PLK-1 recruitment analysis

    PMID:32515113 PMID:36736323 PMID:37067150 PMID:37295434

    Open questions at the time
    • How oligomerization is spatially restricted to functional centromeres unclear
    • Integration of auto-inhibition with kinase regulation not resolved
  14. 2025 High

    Demonstrated in vivo roles for CENP-C dimerization in epigenetic resetting at fertilization and placed downstream alignment factors in its pathway, extending its function to developmental and effector contexts.

    Evidence Mouse CENP-A-mScarlet live imaging with maternal CENP-C depletion and dimerization mutants; genome-wide Cas9 synthetic-lethal screen with hypomorphic CENP-C identifying KIF18A/CENP-E

    PMID:40997799 PMID:41218610

    Open questions at the time
    • Mechanism of asymmetric maternal CENP-C recruitment to paternal centromeres undefined
    • Direct biochemical link between CENP-C and KIF18A/CENP-E not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CENP-C's multiple regulatory inputs (CDK1, Aurora B, PEST phosphorylation, auto-inhibition, RNA, oligomerization) are temporally integrated to coordinate CENP-A inheritance, CCAN assembly, and outer kinetochore biorientation within a single cell cycle remains unresolved.
  • No unified model linking the distinct phospho-regulated and oligomerization-dependent states
  • Stoichiometry and dynamics of CENP-C at endogenous centromeres incompletely defined
  • Causal role in human disease not established in the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 4 GO:0005198 structural molecule activity 3 GO:0042393 histone binding 3 GO:0060090 molecular adaptor activity 3 GO:0003723 RNA binding 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005694 chromosome 3 GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 1 GO:0005730 nucleolus 1
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-4839726 Chromatin organization 4 R-HSA-1474165 Reproduction 3
Partners
AURKBCENP-ACENP-BCENP-HIKMDNMT3BM18BP1MIS12PLK-1
Complex memberships
CCANkinetochore

Evidence

Reading pass · 58 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 CENP-C is a component of the inner kinetochore plate, as determined by immunoelectron microscopy of HeLa chromosomes using antibodies raised against CENP-C cDNA-encoded fusion proteins. Immunoelectron microscopy, indirect immunofluorescence, immunoblotting Cell High 1339310
1989 CENP-C is present exclusively at active centromeres and is absent from inactive centromeres of stable dicentric chromosomes, suggesting it is a necessary component of functional kinetochores; CENP-C appears confined to the outer centromere in the kinetochore region. Immunofluorescence with specific anti-CENP-C antibodies on dicentric chromosomes Chromosoma High 2475307
1994 Nuclear microinjection of anti-CENP-C antibodies during interphase causes metaphase arrest and reduces kinetochore size (trilaminar structures are reduced in diameter), demonstrating CENP-C is required for establishing/maintaining proper kinetochore size and for the timely metaphase-to-anaphase transition. Nuclear microinjection of antibodies, immunoelectron microscopy The Journal of cell biology High 8175879
1994 CENP-C is a DNA-binding protein; an internal ~101 amino acid stretch constitutes its DNA-binding domain, demonstrated by Southwestern blotting of recombinant CENP-C expressed in E. coli against human genomic DNA and alphoid DNA subfamilies. Southwestern blotting, recombinant protein expression, truncation analysis Journal of biochemistry Medium 7883764
1995 The yeast MIF2 protein (CENP-C ortholog) interacts genetically with CEP1/CBF1, NDC10/CBF2, and CEP3/CBF3B at the centromere; mif2 mutations lie within regions homologous to CENP-C, establishing functional and structural conservation between yeast and mammalian centromeres. Genetic epistasis, synthetic lethality screens, minichromosome stability assays Molecular biology of the cell High 7579695
1995 CENP-C has an autonomous centromere-targeting domain located in the central region of the protein, which overlaps with its DNA-binding domain, as defined by truncation mutant analysis in vivo and in vitro. In vivo expression of truncation mutants, in vitro DNA-binding assays Molecular and cellular biology High 8668174
1995 CENP-C and CENP-E localize exclusively to active centromeres (not inactive centromeres) in dicentric Robertsonian translocations, establishing that at least two centromeric proteins are required for human centromeric function. Immunofluorescence combined with FISH on dicentric chromosomes Human molecular genetics High 8634687
1995 The Mif2 homology domain in the central region of CENP-C is required for centromere assembly; mutations within this domain impair CENP-C kinetochore localization. The N-terminus of CENP-C is required for protein destruction and renders otherwise stable proteins unstable. In vivo expression of CENP-C mutants, centromere targeting assays Molecular biology of the cell Medium 7579707
1996 CENP-C interacts with nucleolar transcription factors UBF1 and UBF2 through its C-terminal third, as identified by affinity chromatography and confirmed by co-localization of a subset of CENP-C and UBF at nucleoli in interphase HeLa cells. Affinity chromatography, microsequence analysis, immunofluorescence co-localization The Journal of biological chemistry Medium 8702533
1997 Human CENP-C has three functional units: an N-terminal oligomerization domain (capable of dimer and tetramer formation by crosslinking), an internal DNA-binding domain (with core and flanking stabilizing elements), and a C-terminal dimerization domain (forming exclusively dimers), as defined by biochemical analysis of expressed fragments. Chemical crosslinking, gel filtration, Southwestern blotting Chromosome research Medium 9146917
1997 CENP-C loss of function (conditional fusion to mouse steroid receptor in DT40 cells) causes arrest at the metaphase/anaphase junction followed by apoptosis, demonstrating CENP-C is required for anaphase progression or centromere signaling. Conditional gene targeting, live cell observation, DT40 chicken cells Human molecular genetics High 9361037
1998 CENP-C interacts with HDaxx (a death domain-binding protein) through the N-terminal 315 amino acids of CENP-C and the C-terminal 104 amino acids of HDaxx; this interaction is interphase-specific and they co-localize at discrete nuclear spots in interphase HeLa cells. Yeast two-hybrid, immunofluorescence co-localization Journal of cell science Medium 9645950
1999 Herpes simplex virus immediate-early protein Vmw110 (ICP0) causes proteasome-dependent loss of CENP-C from centromeres during infection (via its RING finger domain), resulting in ultrastructural kinetochore disruption, mitotic arrest, and abnormal cytokinesis. Viral infection, proteasome inhibitor treatment, immunofluorescence, electron microscopy The EMBO journal High 10075924
1999 CENP-C is necessary but not sufficient for formation of a functional centromere; its removal disassembles the centromere protein complex and blocks cells at metaphase-anaphase junction, while overexpression of CENP-C does not associate with ZW10 and causes segregation errors. Conditional gene disruption, inducible overexpression, immunofluorescence in DT40 cells The EMBO journal High 10428958
2001 CENP-H is required for centromere targeting of CENP-C but not CENP-A in vertebrate cells, establishing a hierarchical assembly order at the centromere: CENP-A → CENP-H → CENP-C. Conditional knockout in DT40 cells, immunocytochemistry The EMBO journal High 11500386
2001 C. elegans HCP-4/CENP-C localizes to centromeres in a CENP-A (HCP-3)-dependent manner, and its loss of function by RNAi results in failure of sister centromere resolution and failure to form functional kinetochores; HCP-4 and HCP-3 are both required for localization of HCP-1 (CENP-F-like), defining an ordered assembly pathway. RNAi, immunofluorescence localization in C. elegans The Journal of cell biology High 11402064
2001 A SUMO-1 gene suppresses the temperature-sensitive phenotype of a CENP-C mutant in DT40 cells, suggesting that SUMO-1 is involved in centromere function in vertebrate cells through a pathway involving CENP-C. cDNA library suppressor screen, temperature-sensitive CENP-C mutants in DT40 cells Nucleic acids research Medium 11557811
2002 CENP-C binds alpha-satellite DNA in vivo selectively; the region between amino acids 410 and 537 is required for this in vivo DNA binding; CENP-C and CENP-B associate with the same types of alpha-satellite arrays but in distinct non-overlapping centromere domains. Chromatin immunoprecipitation (ChIP), immunofluorescence, ultrastructural analysis Journal of cell science High 12006616
2002 CENP-C inactivation in DT40 cells causes mitotic delay, impairs the Mad2 spindle checkpoint pathway (~60% of CENP-C-deficient cells lack Mad2 signals after nocodazole), and causes significant reduction in Mis12 complex proteins at centromeres; CENP-C centromere localization in interphase requires the CENP-H complex. Conditional knockout in DT40 cells, immunofluorescence, live-cell microscopy Molecular biology of the cell High 17392512
2002 PARP-2 does not interact with CENP-C as determined by co-immunoprecipitation, distinguishing CENP-C from CENP-A and CENP-B which do interact with PARP-2. Co-immunoprecipitation Human molecular genetics Medium 12217960
2002 Human CENP-C contains two distinct centromere-targeting domains: one in the central region (aa 426-537) and one in the C-terminal region (aa 638-943), both capable of binding alpha-satellite DNA in vivo. Immunofluorescence of truncation mutants, ChIP Journal of structural biology Medium 12490152
2003 CENP-B interacts directly with CENP-C; the CENP-C domains required for this interaction overlap with three Mif2 homologous regions and are also involved in centromere assembly. Overproduction of CENP-B truncants lacking CENP-C interaction domains causes abnormal CENP-C domain duplication and cell cycle delay. Yeast two-hybrid, domain truncation analysis, immunofluorescence The Journal of biological chemistry Medium 14612452
2004 CENP-C can be sumoylated in vitro by SUMO-1 and SUMO-2; sumoylation occurs at multiple lysine residues including sites outside the perfect consensus motif, within regions overlapping the DNA-binding and centromere localization domains. In vitro sumoylation reconstitution, tandem mass spectrometry identification of sumoylated isopeptides The Journal of biological chemistry Medium 15272016
2007 Drosophila CENP-C is required for normal kinetochore attachment to the spindle; it was identified through genetic interaction with separase regulatory subunits Pimples/securin and Three rows, and its centromere localization domain contains a diverged CENPC motif. Genetic modifier screen, in vivo imaging, domain analysis Genes & development Medium 16140985
2007 Drosophila CID (CENP-A) and CENP-C are incorporated into centromeres during anaphase in early embryos; this incorporation is independent of DNA synthesis and spindle pulling forces but strictly coupled to mitotic progression. Quantitative fluorescence measurements in living embryos using fluorescent fusion proteins Current biology High 17222555
2007 Caspase-7 (activated downstream of death receptor-induced caspase-8) cleaves CENP-C and INCENP, causing their mislocalization and subsequent mislocalization of Aurora B kinase from centromeres; expression of non-cleavable CENP-C prevents passenger complex mislocalization after caspase activation. Biochemical caspase cleavage assays, site-directed mutagenesis, immunofluorescence Molecular biology of the cell High 17287400
2009 CENP-C recruits the Mis12/MIND complex and CENP-K to kinetochores via its N-terminal domain; immunodepletion of CENP-C from Xenopus metaphase egg extract prevents kinetochore formation on sperm chromatin; CENP-C mutants that localize to centromeres but fail to recruit Mis12/MIND complex cannot support kinetochore assembly. Xenopus egg extract immunodepletion, in vitro complementation with mutant CENP-C, immunofluorescence Molecular biology of the cell High 19641019
2009 DNMT3B interacts directly with CENP-C (identified by yeast two-hybrid and confirmed by co-immunoprecipitation in mammalian cells); CENP-C recruits DNMT3B and DNA methylation to centromeric and pericentromeric satellite repeats; loss of CENP-C reduces DNA methylation at centromeres, alters the histone code, and increases chromosome missegregation and centromeric repeat transcription. Yeast two-hybrid, co-immunoprecipitation, siRNA knockdown, bisulfite sequencing, ChIP Human molecular genetics High 19482874
2009 The C-terminal Mif2p homology domain II of CENP-C targets the centromere and contacts alpha-satellite DNA; domain III mediates homo-dimerization, homo-oligomerization, and interaction with CENP-A and histone H3. Immunofluorescence, ChIP, co-immunoprecipitation, bimolecular fluorescence complementation PloS one Medium 19503796
2009 Fission yeast CENP-C (Cnp3) acts as a scaffold recruiting Fta1/CENP-L (primary direct effector) for mitotic kinetochore function; Cnp3 also recruits Pcs1 to prevent merotelic attachment; in meiosis, Cnp3 associates with and recruits Moa1 for meiotic mono-orientation of kinetochores. Yeast genetic and biochemical analyses, epistasis, ectopic localization Developmental cell High 19758558
2010 Maize CENPC DNA binding is mediated by a 122 amino acid domain and is stabilized by single-stranded RNA; long single-stranded nucleic acids promote CENPC binding to DNA. Removal of this binding module causes partial delocalization of CENPC in vivo. In vitro DNA/RNA binding assays, domain truncation, in vivo localization with mutants PLoS genetics Medium 20140237
2010 Drosophila Cal1 links CENP-A/Cid and CENP-C by binding their N- and C-terminal domains respectively (shown by yeast three-hybrid); Cal1 limits centromeric deposition of CENP-A/Cid and CENP-C during mitotic exit; both Cal1 domains are required together for centromere function. Yeast three-hybrid, quantitative in vivo fluorescence imaging Journal of cell science High 20940262
2011 The N-terminal region of Drosophila CENP-C is sufficient to recruit all KMN network components (Mis12 complex, Ndc80 complex, Spc105/KNL1); the Mis12 complex component Nnf1 directly interacts with CENP-C in vitro; targeting the CENP-C N-terminus to centrosomes redirects KMN proteins away from kinetochores, causing mitotic defects. In vitro binding assay, ectopic targeting assay (centrosome targeting), immunofluorescence in Drosophila cells Current biology High 21353555
2011 A conserved N-terminal motif of vertebrate Cenp-C binds directly and with high affinity to the Mis12 complex, linking the inner and outer kinetochore; expression of the isolated N-terminal Cenp-C motif in HeLa cells prevents outer kinetochore assembly, causes chromosome missegregation, and impairs spindle assembly checkpoint. Direct binding assay (biochemical reconstitution), dominant-negative expression in HeLa cells, immunofluorescence Current biology High 21353556
2011 CENP-C recruits M18BP1 (Mis18 complex component) to centromeres to promote CENP-A chromatin assembly; depletion of CENP-C prevents M18BP1 targeting to metaphase centromeres and inhibits CENP-A assembly; M18BP1 directly binds CENP-C through conserved domains. siRNA depletion, in vitro direct binding assay, immunofluorescence The Journal of cell biology High 21911481
2012 M18BP1 interacts with CENP-C through a central SANT domain region of M18BP1 and the C-terminus of CENP-C; CENP-C knockdown reduces M18BP1 centromeric association and lowers CENP-A levels at centromeres. Interaction screen, domain mapping, siRNA knockdown, immunofluorescence in mouse ESCs Nucleus Medium 22540025
2013 CENP-C recognizes the CENP-A nucleosome by binding a hydrophobic region in the CENP-A tail and docking onto the acidic patch of histones H2A and H2B; this mechanism is used by both the CENP-C motif and the broader conserved central region; the mechanism is conserved across species. Crystal structure determination, NMR, mutagenesis, biochemical binding assays Science High 23723239
2015 CENP-C binds CENP-A nucleosomes (using purified components) and reshapes the octameric histone core: it rigidifies both surface and internal nucleosome structure and modulates terminal DNA wrapping to match the loose wrap found on native CENP-A nucleosomes. CENP-C depletion leads to rapid removal of CENP-A from centromeres. In vitro reconstitution with purified components, fluorescence lifetime imaging, single-molecule FRET, CENP-C depletion in cells Science High 25954010
2015 The PEST domain in the N-terminal half of CENP-C directly interacts with the CENP-HIKM subcomplex, and this interaction is required for kinetochore localization of CENP-HIKM and CENP-TW; CENP-C acts as a blueprint for CCAN assembly. Biochemical reconstitution, domain mapping, cellular rescue assays, immunofluorescence The Journal of cell biology High 26124289
2015 CENP-C and CENP-T independently recruit the KMN network to kinetochores via distinct mechanisms and regulatory controls: CENP-C recruits Ndc80 through KNL1 and Mis12 interactions (regulated by Aurora B), while CENP-T directly interacts with Ndc80 (regulated by CDK). Ectopic chromosomal targeting assays in human cells, immunofluorescence Current biology High 25660545
2015 CENP-C depletion leads to increased centromere DNA aberrations (sister chromatid exchanges at centromeres), indicating CENP-C maintains centromere repeat integrity independently of its role in chromosome segregation. CO-FISH (chromosome orientation FISH), siRNA depletion, structured illumination microscopy PNAS Medium 28167779
2015 CENP-C and CENP-I are key factors connecting kinetochore to CENP-A assembly; tethering various kinetochore components to an ectopic array recruits CENP-C and subsequently M18BP1; CENP-I can also recruit M18BP1 downstream of CENP-C to enhance M18BP1 assembly at centromeres. Tethering assay with tetR-fusion proteins on synthetic alphoid array HACs, immunofluorescence Journal of cell science Medium 26527398
2016 Crystal structure of human MIS12C in complex with a CENP-C fragment reveals the structural basis of the CENP-C–Mis12 interaction; Aurora B kinase phosphorylation of CENP-C regulates this interaction, allowing construction of a near-complete structural model of the KMN assembly. X-ray crystallography, biochemical binding assays, Aurora B kinase phosphorylation assays Cell High 27881301
2016 CENP-C directs a structural transition in CENP-A nucleosomes predominantly through lateral sliding of DNA gyres (gyre sliding), returning them toward canonical nucleosome DNA positions, as measured by single-molecule FRET. Single-molecule FRET with recombinant human histones and centromere DNA 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 FISH, antisense oligonucleotide depletion, immunofluorescence Developmental cell Medium 28787590
2017 Yeast Mif2/CENP-C uses a contiguous DNA- and histone-binding domain (DHBD) containing the CENP-C motif, an AT-hook, and RK clusters to contact both Cse4/CENP-A residues and AT-rich centromere DNA simultaneously; human CENP-C has two related DHBDs that preferentially bind higher AT content DNA. Biochemical binding assays, mutational analysis, structural analysis Genes & development High 29074736
2017 Aurora B kinase phosphorylates the N-terminal region (Thr28) of S. pombe CENP-C (Cnp3), impairing its interaction with the Mis12 complex; a phosphomimetic mutant causes defective chromosome segregation due to improper kinetochore assembly. Kinase assay, co-immunoprecipitation, crystal structure of Mis12-Nnf1 complex, mutant expression in S. pombe PNAS High 29180432
2019 CDK1 phosphorylates the C-terminal region of CENP-C (at conserved sites), facilitating its binding to CENP-A nucleosomes in vitro and in vivo; this CENP-A binding promotes CENP-C kinetochore localization during mitosis, and the CENP-A–CENP-C interaction is critical for long-term viability in human RPE-1 cells. In vitro kinase assay (CDK1), Phos-tag SDS-PAGE, co-immunoprecipitation, immunofluorescence in chicken and human cells, cell viability assays The Journal of cell biology High 31676716
2019 Human CENP-C central region (CENP-CCR) and CENP-C motif both bind exclusively to CENP-A nucleosomes in vitro; CENP-CCR binds with high affinity through CENP-AV532 and CENP-AV533 (extended hydrophobic area); CENP-CCR binding destabilizes the H2A C-terminal tail (further exacerbating loose DNA wrapping) and rigidifies H4 N-terminal tail in the conformation favoring H4K20 monomethylation. Cryo-EM structure of CENP-A nucleosome, in vitro binding assays, mutagenesis EMBO reports High 31475439
2020 Mif2/CENP-C exhibits auto-inhibition: wild-type Mif2 is attenuated in binding the Mtw1 complex, and binding Cse4/CENP-A nucleosomes overcomes this inhibition; a Mif2 mutant bypassing Cse4 requirement for Mtw1 binding causes mis-localization of the Mtw1 complex and chromosome segregation defects in vivo. In vitro binding assays with reconstituted nucleosomes, yeast genetics, immunofluorescence The EMBO journal High 32515113
2022 lncRNA CCTT recruits CENP-C to centromeric DNA via RNA-DNA triplex formation and a direct RNA-protein interaction with CENP-C; CCTT loss triggers mitotic errors and aneuploidy, and CCTT localizes to all centromeres. RNA immunoprecipitation, RNA-DNA triplex assay, siRNA/shRNA depletion, immunofluorescence, FISH Molecular cell Medium 36332605
2023 CENP-C undergoes self-oligomerization through its C-terminal Cupin domain (demonstrated by structural and biochemical analyses of chicken and human CENP-C); this oligomerization is vital for CENP-C function, centromeric localization of CCAN proteins, and centromeric chromatin organization. Crystal structure of Cupin domain, biochemical self-oligomerization assays, mutagenesis, immunofluorescence in chicken cells Molecular cell High 37295434
2023 In C. elegans oocytes, CENP-C (HCP-4) directly recruits PLK-1 to the chromosome arm during meiosis (independent of BUB-1); disruption of the CENP-C–PLK-1 interaction leads to imbalance in kinetochore components and chromosome congression defects without affecting CDC-20 recruitment. Live imaging, biochemical interaction assays, RNAi, degron-mediated depletion in C. elegans oocytes eLife High 37067150
2023 Multi-site phosphorylation of the PEST region of yeast Mif2/CENP-C enhances inner kinetochore assembly; eliminating PEST phosphorylation sites progressively impairs cellular fitness and causes lethality in cells lacking otherwise non-essential inner kinetochore factors. Yeast genetics, phosphorylation-site mutagenesis, genetic interaction analysis Current biology Medium 36736323
2024 In C. elegans embryos, CENP-C targets PLK-1 to the inner kinetochore during prometaphase and metaphase; disruption of the CENP-C–PLK-1 interaction causes kinetochore component imbalance and chromosome congression defects distinct from the effects of BUB-1-targeted PLK-1 (which controls CDC-20 recruitment and SAC). Engineered protein interaction mutants, live imaging, immunofluorescence in C. elegans embryos Journal of cell science High 39355896
2024 The CENP-C–Mis12 complex (Mis12C) interaction facilitates centromeric recruitment of Aurora B; Aurora B in turn reinforces the CENP-C–Mis12C interaction, creating a positive regulatory loop that ensures kinetochore biorientation and error correction. Immunofluorescence, co-immunoprecipitation, CENP-C mutant analysis in human RPE-1 cells and mouse models Life science alliance Medium 39433344
2025 Maternal CENP-C is recruited asymmetrically to paternal centromeres in the zygote, and this recruitment is required to equalize CENP-A levels between maternal and paternal centromeres before first mitosis; disruption of CENP-C dimerization impairs CENP-A equalization and chromosome segregation. CENP-A-mScarlet mouse model, live imaging, maternal CENP-C depletion, dimerization-disrupting mutants Developmental cell High 40997799
2025 KIF18A promotes chromosome alignment in cooperation with CENP-E downstream of CENP-C; a genome-wide Cas9 screen using a hypomorphic CENP-C mutant identified KIF18A as synthetic lethal, with the synthetic defect caused by reduction in CENP-E function in the CENP-C mutant background. Genome-wide Cas9 functional genetics screen, synthetic lethality, immunofluorescence Cell reports Medium 41218610

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 370 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 300 17222555
1989 Visualization of centromere proteins CENP-B and CENP-C on a stable dicentric chromosome in cytological spreads. Chromosoma 283 2475307
2013 A conserved mechanism for centromeric nucleosome recognition by centromere protein CENP-C. Science (New York, N.Y.) 277 23723239
2011 CENP-C is a structural platform for kinetochore assembly. Current biology : CB 225 21353555
2011 Direct binding of Cenp-C to the Mis12 complex joins the inner and outer kinetochore. Current biology : CB 222 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 196 8634687
2011 CENP-C recruits M18BP1 to centromeres to promote CENP-A chromatin assembly. The Journal of cell biology 188 21911481
2015 Chromosomes. CENP-C reshapes and stabilizes CENP-A nucleosomes at the centromere. Science (New York, N.Y.) 182 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
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 140 26124289
2016 Structure of the MIS12 Complex and Molecular Basis of Its Interaction with CENP-C at Human Kinetochores. Cell 133 27881301
2015 Distinct organization and regulation of the outer kinetochore KMN network downstream of CENP-C and CENP-T. Current biology : CB 116 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
2009 CENP-C functions as a scaffold for effectors with essential kinetochore functions in mitosis and meiosis. Developmental cell 99 19758558
1999 A maize homolog of mammalian CENPC is a constitutive component of the inner kinetochore. The Plant cell 97 10402425
2017 Integrity of the human centromere DNA repeats is protected by CENP-A, CENP-C, and CENP-T. Proceedings of the National Academy of Sciences of the United States of America 96 28167779
1999 CENP-C is necessary but not sufficient to induce formation of a functional centromere. The EMBO journal 94 10428958
1997 Efficient conditional mutation of the vertebrate CENP-C gene. Human molecular genetics 92 9361037
2001 HCP-4, a CENP-C-like protein in Caenorhabditis elegans, is required for resolution of sister centromeres. The Journal of cell biology 89 11402064
2005 Genetic interactions of separase regulatory subunits reveal the diverged Drosophila Cenp-C homolog. Genes & development 86 16140985
2002 Poly(ADP-ribose) polymerase 2 localizes to mammalian active centromeres and interacts with PARP-1, Cenpa, Cenpb and Bub3, but not Cenpc. Human molecular genetics 80 12217960
1994 Human centromere protein C (CENP-C) is a DNA-binding protein which possesses a novel DNA-binding motif. Journal of biochemistry 80 7883764
2010 Detrimental incorporation of excess Cenp-A/Cid and Cenp-C into Drosophila centromeres is prevented by limiting amounts of the bridging factor Cal1. Journal of cell science 77 20940262
1995 Sequence similarities between the yeast chromosome segregation protein Mif2 and the mammalian centromere protein CENP-C. Gene 72 7628703
2007 Co-localization of CENP-C and CENP-H to discontinuous domains of CENP-A chromatin at human neocentromeres. Genome biology 69 17651496
1995 Further evidence that CENP-C is a necessary component of active centromeres: studies of a dic(X; 15) with simultaneous immunofluorescence and FISH. Human molecular genetics 69 7757082
2012 The cell cycle timing of centromeric chromatin assembly in Drosophila meiosis is distinct from mitosis yet requires CAL1 and CENP-C. PLoS biology 68 23300382
2016 CENP-C directs a structural transition of CENP-A nucleosomes mainly through sliding of DNA gyres. Nature structural & molecular biology 66 26878239
2002 CENP-C binds the alpha-satellite DNA in vivo at specific centromere domains. Journal of cell science 63 12006616
2015 Dynamic changes in CCAN organization through CENP-C during cell-cycle progression. Molecular biology of the cell 59 26354420
2019 CENP-C unwraps the human CENP-A nucleosome through the H2A C-terminal tail. EMBO reports 57 31475439
2003 CENP-B interacts with CENP-C domains containing Mif2 regions responsible for centromere localization. The Journal of biological chemistry 57 14612452
1997 Characterization of internal DNA-binding and C-terminal dimerization domains of human centromere/kinetochore autoantigen CENP-C in vitro: role of DNA-binding and self-associating activities in kinetochore organization. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 57 9146917
2015 CENP-C and CENP-I are key connecting factors for kinetochore and CENP-A assembly. Journal of cell science 54 26527398
2009 The C-terminal domain of CENP-C displays multiple and critical functions for mammalian centromere formation. PloS one 49 19503796
2019 CDK1-mediated CENP-C phosphorylation modulates CENP-A binding and mitotic kinetochore localization. The Journal of cell biology 48 31676716
2017 Molecular basis of CENP-C association with the CENP-A nucleosome at yeast centromeres. Genes & development 48 29074736
2004 In vitro modification of human centromere protein CENP-C fragments by small ubiquitin-like modifier (SUMO) protein: definitive identification of the modification sites by tandem mass spectrometry analysis of the isopeptides. The Journal of biological chemistry 45 15272016
2001 Creation and characterization of temperature-sensitive CENP-C mutants in vertebrate cells. Nucleic acids research 43 11557811
1996 Human homolog of Drosophila heterochromatin-associated protein 1 (HP1) is a DNA-binding protein which possesses a DNA-binding motif with weak similarity to that of human centromere protein C (CENP-C). Journal of biochemistry 43 8864858
1995 Domains required for CENP-C assembly at the kinetochore. Molecular biology of the cell 40 7579707
1996 Specific interaction between human kinetochore protein CENP-C and a nucleolar transcriptional regulator. The Journal of biological chemistry 37 8702533
2008 Observation of unusual mass transport in solid hcp (4)He. Physical review letters 33 18643513
2002 In vivo functional dissection of human inner kinetochore protein CENP-C. Journal of structural biology 31 12490152
2023 Centromere/kinetochore is assembled through CENP-C oligomerization. Molecular cell 29 37295434
2005 HCP-4/CENP-C promotes the prophase timing of centromere resolution by enabling the centromere association of HCP-6 in Caenorhabditis elegans. Molecular and cellular biology 28 15767665
2013 Centromere proteins CENP-C and CAL1 functionally interact in meiosis for centromere clustering, pairing, and chromosome segregation. Proceedings of the National Academy of Sciences of the United States of America 27 24248385
2010 Drosophila CENP-C is essential for centromere identity. Chromosoma 26 20862486
2015 Possible identification of CENP-C in fish and the presence of the CENP-C motif in M18BP1 of vertebrates. F1000Research 24 27127616
2002 Mutational analysis of the central centromere targeting domain of human centromere protein C, (CENP-C). Experimental cell research 24 11925107
2023 BUB-1 and CENP-C recruit PLK-1 to control chromosome alignment and segregation during meiosis I in C. elegans oocytes. eLife 20 37067150
2022 LncRNA CCTT-mediated RNA-DNA and RNA-protein interactions facilitate the recruitment of CENP-C to centromeric DNA during kinetochore assembly. Molecular cell 20 36332605
2017 Phosphorylation of CENP-C by Aurora B facilitates kinetochore attachment error correction in mitosis. Proceedings of the National Academy of Sciences of the United States of America 20 29180432
2021 CENP-C functions in centromere assembly, the maintenance of CENP-A asymmetry and epigenetic age in Drosophila germline stem cells. PLoS genetics 19 34014920
2015 The distinct functions of CENP-C and CENP-T/W in centromere propagation and function in Xenopus egg extracts. Nucleus (Austin, Tex.) 19 25569378
1994 Sequence homologies and linkage group conservation of the human and mouse Cenpc genes. Genomics 19 7959789
2020 Auto-inhibition of Mif2/CENP-C ensures centromere-dependent kinetochore assembly in budding yeast. The EMBO journal 17 32515113
2019 Structures of CENP-C cupin domains at regional centromeres reveal unique patterns of dimerization and recruitment functions for the inner pocket. The Journal of biological chemistry 14 31366733
1996 Sheep CENPB and CENPC genes show a high level of sequence similarity and conserved synteny with their human homologs. Cytogenetics and cell genetics 14 8893808
2007 Death receptor-induced apoptosis reveals a novel interplay between the chromosomal passenger complex and CENP-C during interphase. Molecular biology of the cell 13 17287400
1999 Visualization of prekinetochore locus on the centromeric region of highly extended chromatin fibers: does kinetochore autoantigen CENP-C constitute a kinetochore organizing center? Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 12 10219728
2018 CENP-C/H/I/K/M/T/W/N/L and hMis12 but not CENP-S/X participate in complex formation in the nucleoplasm of living human interphase cells outside centromeres. PloS one 11 29509805
2005 Comparison of Dam tagging and chromatin immunoprecipitation as tools for the identification of the binding sites for S. pombe CENP-C. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 11 15791413
1998 Epitope mapping of human centromere autoantigen centromere protein C (CENP-C); heterogeneity of anti-CENP-C response in rheumatic diseases. The Journal of rheumatology 10 9517766
2023 Multi-site phosphorylation of yeast Mif2/CENP-C promotes inner kinetochore assembly. Current biology : CB 8 36736323
2023 A dynamic population of prophase CENP-C is required for meiotic chromosome segregation. PLoS genetics 8 38019881
2016 Nucleolar activity and CENP-C regulate CENP-A and CAL1 availability for centromere assembly in meiosis. Development (Cambridge, England) 8 27095496
2020 Meiotic CENP-C is a shepherd: bridging the space between the centromere and the kinetochore in time and space. Essays in biochemistry 7 32794572
2018 Concurrent Duplication of Drosophila Cid and Cenp-C Genes Resulted in Accelerated Evolution and Male Germline-Biased Expression of the New Copies. Journal of molecular evolution 7 29934734
2015 The human papillomavirus18 E7 protein inhibits CENP-C binding to α-satellite DNA. Virus research 6 25997930
2007 Characterization of a neocentric supernumerary marker chromosome originating from the Xp distal region by FISH, CENP-C staining, and array CGH. Cytogenetic and genome research 6 17268194
1993 Mapping of the human CENP-B gene to chromosome 20 and the CENP-C gene to chromosome 12 by a rapid cycle DNA amplification procedure. Genomics 6 8406460
2022 MEL-28/ELYS and CENP-C coordinately control outer kinetochore assembly and meiotic chromosome-microtubule interactions. Current biology : CB 5 35609608
2009 Characterization of the two centromeric proteins CENP-C and MIS12 in Nicotiana species. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 5 19697146
2001 Gene structure, chromosomal localization and immunolocalization of chicken centromere proteins CENP-C and ZW10. Gene 5 11179694
2024 CENP-C-targeted PLK-1 regulates kinetochore function in C. elegans embryos. Journal of cell science 4 39355896
2018 Fission Yeast CENP-C (Cnp3) Plays a Role in Restricting the Site of CENP-A Accumulation. G3 (Bethesda, Md.) 4 29925533
2017 Nucleoporins NPP-10, NPP-13 and NPP-20 are required for HCP-4 nuclear import to establish correct centromere assembly. Journal of cell science 4 28122936
2024 CENP-C-Mis12 complex establishes a regulatory loop through Aurora B for chromosome segregation. Life science alliance 3 39433344
2025 Centromeric localization of αKNL2 and CENP-C proteins in plants depends on their centromere-targeting domain and DNA-binding regions. Nucleic acids research 2 39718987
2025 Maternal CENP-C restores centromere symmetry in mammalian zygotes to ensure proper chromosome segregation. Developmental cell 2 40997799
2025 Sustainable integrative cell biology: CENP-C is guilty by association. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 2 41288785
2021 Immunization with CENP-C Causes Aberrant Chromosome Segregation during Oocyte Meiosis in Mice. Journal of immunology research 2 33604391
2021 CENP-C Phosphorylation by CDK1 in vitro. Bio-protocol 2 33732767
1996 FISH mapping of centromere protein C (CENPC) on human chromosome 4q31-->q21. Cytogenetics and cell genetics 2 8941372
2025 KIF18A promotes chromosome congression in cooperation with CENP-E downstream of CENP-C. Cell reports 1 41218610
2025 Sustainable integrative cell biology: CENP-C is guilty by association. Chromosoma 1 41288728
2023 Anti-CENP-C Antibody-Based Immunofluorescence Dicentric Assay: Radiation Dose-Response, Validation Studies, and Radiation Dose-Dependency on Sister Centromere Fluorescence. Radiation research 1 36442049
2024 Functional roles of the interaction of Moa1 with CENP-C and Rec8 in meiosis of Schizosaccharomyces pombe. Yi chuan = Hereditas 0 39140145

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