Affinage

CENPA

Histone H3-like centromeric protein A · UniProt P49450

Length
140 aa
Mass
16.0 kDa
Annotated
2026-04-28
100 papers in source corpus 32 papers cited in narrative 32 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CENP-A is the centromere-specific histone H3 variant that epigenetically defines active centromeres and serves as the foundational scaffold for kinetochore assembly. CENP-A forms octameric nucleosomes with distinctive structural features — a short αN helix that generates flexible DNA ends excluding linker histone H1, and a CATD loop that confers specificity for the dedicated chaperone HJURP — which together create an exposed chromatin platform recognized by the constitutive centromere-associated network (CCAN) including CENP-C, CENP-N, CENP-T, and additional subunits that topologically entrap DNA to resist spindle forces (PMID:16622419, PMID:35420891, PMID:27499292). Cell-cycle-restricted deposition of new CENP-A in late mitosis/G1 is enforced by a two-step licensing mechanism in which Plk1 promotes Mis18 complex centromere recruitment (counterbalanced by CDK-mediated inhibition of M18BP1 binding to Mis18α/β) and Cdk1 phosphorylation of CENP-A Ser68 blocks HJURP binding until mitotic exit (PMID:25036634, PMID:28059702, PMID:25556658). Faithful inheritance of centromeric CENP-A through DNA replication requires HJURP acting with the MCM2-7 helicase during S phase, while post-translational modifications including α-amino trimethylation by NRMT, Aurora A phosphorylation at Ser7, CUL4A-mediated K124 ubiquitylation, and interaction with m6A-modified centromeric RNA further regulate centromere maintenance and chromosome segregation fidelity (PMID:30293838, PMID:28266506, PMID:29760389, PMID:27052173, PMID:39305902).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2000 High

    Establishing that CENP-A is the upstream organizer of centromeric chromatin answered whether centromere identity depends on a single histone variant: Cenpa-null mouse embryos lose CENP-B and CENP-C from centromeres and die early in development, proving CENP-A is essential and epistatic to other centromere proteins.

    Evidence Gene-targeted knockout mouse with immunofluorescence of null embryos

    PMID:10655499

    Open questions at the time
    • Downstream mechanism by which CENP-A loss disperses CENP-C was not resolved
    • Whether CENP-A is sufficient (not just necessary) for centromere identity was untested
  2. 2001 Medium

    Identifying mitosis-specific phosphorylation of CENP-A revealed that this histone variant undergoes cell-cycle-regulated modification analogous to H3 Ser10 phosphorylation, suggesting kinetochore-specific signaling layers.

    Evidence Phospho-specific antibodies with cell-cycle immunofluorescence in human cells

    PMID:11171370

    Open questions at the time
    • The kinase responsible was not identified in this study
    • Functional consequence of this phosphorylation event was not demonstrated
  3. 2006 High

    Defining the CENP-A nucleosome-associated complex (NAC/CAD) answered how centromeric chromatin nucleates kinetochore assembly: CENP-A nucleosomes directly recruit a proximal complex of CENP-C, CENP-N, CENP-T, CENP-H, CENP-M, and CENP-U, upon which distal components assemble, and disruption causes chromosome segregation errors.

    Evidence Affinity purification/mass spectrometry, reciprocal Co-IP, siRNA knockdown with mitotic phenotype readout

    PMID:16622419

    Open questions at the time
    • Structural basis of NAC-CENP-A nucleosome contacts was unknown
    • How individual NAC subunits recognize CENP-A versus H3 nucleosomes was not resolved
  4. 2011 High

    Structural and functional dissection of HJURP-mediated CENP-A deposition answered how CENP-A is distinguished from canonical H3 for centromere targeting: the HJURP crystal structure revealed a β-sheet domain capping the CENP-A–H4 DNA-binding surface via CENP-A-specific contacts, while CENP-C was shown to recruit the Mis18/M18BP1 licensing complex to prime deposition, and CCAN components were separated into centromere-establishing versus kinetochore-recruiting roles.

    Evidence X-ray crystallography of HJURP–CENP-A–H4 complex; direct binding assays and siRNA depletion for CENP-C–M18BP1 interaction; chromosome engineering with ectopic targeting in DT40 cells

    PMID:21478274 PMID:21911481 PMID:23277427

    Open questions at the time
    • How HJURP is released after deposition was not resolved
    • Structure of the complete Mis18–HJURP–CENP-A loading intermediate was lacking
  5. 2014 High

    Elucidating the cell-cycle licensing mechanism answered why CENP-A deposition is restricted to late mitosis/G1: Plk1 promotes Mis18 complex centromere recruitment while CDK opposes it, and separately Cdk1 phosphorylates CENP-A Ser68 to block HJURP binding until PP1α-mediated dephosphorylation at mitotic exit, creating a two-tiered temporal gate.

    Evidence Chemical inhibition and kinase-dead mutants of Plk1/CDK with CENP-A deposition assays; in vitro kinase assays with phospho-specific antibodies and Co-IP

    PMID:25036634 PMID:25556658

    Open questions at the time
    • How Plk1 is recruited to centromeres for Mis18 licensing was not fully defined
    • Whether additional phosphatases contribute to CENP-A Ser68 dephosphorylation was untested
  6. 2015 High

    Determining how CENP-B and domain requirements stabilize CENP-A and recruit CCAN during centromere establishment answered what features of CENP-A nucleosomes control initial versus maintenance centromere identity: CENP-B directly binds CENP-A–H4 and stabilizes CENP-A on alphoid DNA, while both the N-terminal tail and the CATD are required for initial CENP-C/CENP-T recruitment.

    Evidence In vitro reconstitution and pulldown assays for CENP-B; LacI-LacO tethering of H3-CENP-A chimeras with immunofluorescence

    PMID:25713413 PMID:25916850

    Open questions at the time
    • Structural basis of CENP-B–CENP-A–H4 interaction at atomic resolution was missing
    • Whether CENP-B stabilization is required at neocentromeres (which lack CENP-B boxes) was unresolved
  7. 2016 High

    Characterizing the flexible DNA-end architecture and post-translational modification landscape of CENP-A nucleosomes answered how centromeric chromatin is structurally distinguished from bulk chromatin: the short αN helix prevents H1 binding and is essential for kinetochore protein localization; K124 ubiquitylation by CUL4A is inherited through divisions and required for new CENP-A recruitment; and KAT7 acetylation antagonizes heterochromatin to facilitate CENP-A assembly.

    Evidence Cryo-EM and biochemical H1-binding assays with αN domain swaps; in vivo ubiquitylation tracking with dimerization mutants; KAT7 KO and tethering assays with ChIP

    PMID:27052173 PMID:27270040 PMID:27499292

    Open questions at the time
    • Whether αN-dependent H1 exclusion operates in all cell types was not tested
    • The deubiquitylase counterbalancing K124 ubiquitylation was not identified
  8. 2017 High

    Reconstituting the Mis18–HJURP interaction and defining CDK1 control of M18BP1 answered how the loading machinery is biochemically assembled and cell-cycle-gated: two HJURP repeats bind the 4:2:2 Mis18α:Mis18β:M18BP1 hexamer via sites gated by Mis18α N-terminal tails, and CDK1 phosphorylation of M18BP1 destabilizes its binding to the Mis18αβ core, restricting complex formation to G1.

    Evidence Photo-cross-linking and mutagenesis of Mis18–HJURP interface; biochemical reconstitution of Mis18 complex with CDK1 phosphomutant analysis

    PMID:28059702 PMID:31492860

    Open questions at the time
    • How dephosphorylation of M18BP1 is temporally coordinated with Plk1 activity was not addressed
    • Whether the two HJURP repeats deposit two CENP-A–H4 dimers simultaneously was not resolved
  9. 2018 High

    Discovering HJURP's S-phase function with MCM2 answered how parental CENP-A nucleosomes survive replication fork passage: HJURP transiently associates with centromeres during S phase, co-purifies with the MCM2-7 helicase, and simultaneously binds CENP-A and MCM2, functioning as an inheritance factor rather than solely a deposition chaperone.

    Evidence BioID proximity labeling, Co-IP, siRNA depletion, and in vitro binding assays

    PMID:30293838

    Open questions at the time
    • Whether HJURP recycles CENP-A to the same or sister centromere after fork passage was unknown
    • Structural basis of the ternary HJURP–CENP-A–MCM2 complex was not determined
  10. 2019 High

    High-resolution cryo-EM structures of the CENP-A nucleosome and CENP-C-bound CENP-A nucleosome answered how centromeric nucleosomes are conformationally reshaped by CCAN binding: CENP-C binding destabilizes the H2A C-terminal tail to further loosen DNA wrapping and rigidifies the H4 N-terminal tail in a conformation favoring H4K20me1, while tri-nucleosome structures showed CENP-A creates an untwisted fiber exposing it to centromere proteins.

    Evidence Cryo-EM at 2.6 Å of CENP-A nucleosome on α-satellite DNA; cryo-EM of CENP-C–CENP-A nucleosome complex with mutagenesis; cryo-EM of reconstituted H3-CENP-A-H3 tri-nucleosomes

    PMID:31127102 PMID:31475439 PMID:31711756

    Open questions at the time
    • How CENP-C-induced H4K20me1 is read downstream was not established
    • Whether the tri-nucleosome architecture is maintained in native centromeric chromatin fibers was not verified
  11. 2020 Medium

    Identifying Spt6 as a CENP-A retention factor during centromeric transcription answered how active transcription through centromeres avoids evicting CENP-A: Spt6 directly binds CENP-A and prevents its loss during transcription, with phosphomimetic CENP-A mutations reducing Spt6 association and centromeric CENP-A retention.

    Evidence Direct binding assay between Spt6 and dCENP-A/CENP-A, phosphomutant analysis in Drosophila and human cells

    PMID:32522980

    Open questions at the time
    • The kinase phosphorylating CENP-A to regulate Spt6 binding was not identified in human cells
    • Whether Spt6-mediated retention is coupled to HJURP-mediated recycling was unknown
  12. 2022 High

    The cryo-EM structure of the complete CCAN bound to a CENP-A nucleosome answered how the inner kinetochore withstands spindle forces: CCAN makes edge-on contacts with the CENP-A nucleosome, linker DNA threads through the CENP-LN channel, and CENP-TWSX partially wraps DNA, topologically entrapping the centromeric fiber.

    Evidence Cryo-EM of reconstituted full CCAN–CENP-A nucleosome complex

    PMID:35420891

    Open questions at the time
    • How dynamic remodeling of CCAN–nucleosome contacts occurs during the tension cycle was not addressed
    • Whether the topological entrapment model applies equally at neocentromeres was untested
  13. 2024 High

    Discovering CENP-A as an m6A reader of centromeric RNA answered how centromeric transcripts contribute to CENP-A maintenance: m6A-modified cenRNA stabilizes CENP-A at centromeres during S phase via Leu61 and Arg63, and disruption of this interaction causes CENP-A loss and chromosome missegregation.

    Evidence m6A-seq, CENP-A point mutagenesis at L61/R63, ChIP, and chromosome segregation assays in cancer cells

    PMID:39305902

    Open questions at the time
    • The RNA methyltransferase responsible for centromeric m6A deposition was not identified
    • Whether m6A reading cooperates with HJURP-MCM2-mediated S-phase retention was not tested
    • Structural basis of CENP-A–m6A-RNA interaction was not determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions remain regarding how CENP-A inheritance is coordinated across replication, transcription, and post-translational modification pathways, and whether the distinct structural and regulatory mechanisms cooperate or act redundantly to maintain centromere identity through successive cell divisions.
  • No integrated structural model of the HJURP–MCM2–CENP-A–Spt6 handoff during replication-coupled retention
  • Whether m6A-RNA reading and K124 ubiquitylation act in the same or parallel S-phase retention pathways is unknown
  • How CENP-A deposition/maintenance is regulated in meiosis remains poorly characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0042393 histone binding 4 GO:0005198 structural molecule activity 3 GO:0003723 RNA binding 1
Localization
GO:0005694 chromosome 5 GO:0005634 nucleus 2
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-4839726 Chromatin organization 4 R-HSA-69306 DNA Replication 2
Partners
CENPBCENPCCENPNCENPTDAXXHJURPMCM2SUPT6H
Complex memberships
CCAN (constitutive centromere-associated network)CENP-A nucleosome

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 CENP-A nucleosomes directly recruit a proximal CENP-A nucleosome associated complex (NAC) comprising CENP-M, CENP-N, CENP-T, CENP-U(50), CENP-C, and CENP-H; assembly of this NAC is dependent on CENP-M, CENP-N, and CENP-T; seven additional CENP-A nucleosome distal (CAD) components (CENP-K, -L, -O, -P, -Q, -R, -S) assemble on the NAC; disruption of the complex causes chromosome alignment and segregation errors. Affinity purification/mass spectrometry, Co-immunoprecipitation, siRNA knockdown with mitotic phenotype readout Nature cell biology High 16622419
2000 CENP-A (Cenpa) is essential for kinetochore targeting of CENP-C; Cenpa null mouse embryos fail beyond E6.5 and display micronuclei, nuclear bridging, chromatin fragmentation, and dispersal of Cenpb and Cenpc from centromeres, establishing CENP-A as an upstream organizer of centromeric chromatin. Gene targeting (knockout mouse), immunofluorescence of null embryos Proceedings of the National Academy of Sciences of the United States of America High 10655499
2011 Crystal structure of HJURP bound to a CENP-A–H4 heterodimer shows that HJURP's C-terminal β-sheet domain caps the DNA-binding surface of the CENP-A–H4 heterodimer, preventing spontaneous DNA association; a novel surface in CENP-A distinguishes it from H3 for HJURP recognition. X-ray crystallography, in vitro binding assays, mutagenesis Genes & development High 21478274
2011 CENP-C recruits the Mis18 complex protein M18BP1 to centromeres through direct binding via conserved domains in CENP-C; depletion of CENP-C prevents M18BP1 targeting to metaphase centromeres and inhibits CENP-A chromatin assembly. Protein depletion (siRNA), in vitro direct binding assay (pulldown), immunofluorescence The Journal of cell biology High 21911481
2014 Polo-like kinase 1 (Plk1) is required to initiate CENP-A deposition by promoting localization of the Mis18 complex to centromeres; CDK activity inhibits Mis18 complex assembly; these two signals form a two-step licensing mechanism controlling cell-cycle-restricted CENP-A deposition. Chemical inhibition and kinase-dead mutants of Plk1/CDK, immunofluorescence, CENP-A deposition assays in human cells Cell High 25036634
2014 CENP-A is phosphorylated at Ser68 by Cdk1 during early mitosis; this phosphorylation eliminates CENP-A binding to HJURP, preventing premature centromeric loading; dephosphorylation by PP1α at mitotic exit permits HJURP-mediated deposition at centromeres. In vitro kinase assay, phospho-specific antibodies, co-immunoprecipitation, CENP-A loading assays in human cells Developmental cell High 25556658
2012 CENP-A nucleosomes cycle between octameric and tetrameric forms across the human cell cycle: they exist as tetramers after replication and convert to octamers before replication; these structural transitions are accompanied by reversible chaperone binding and chromatin fiber folding changes and modifications within CENP-A and H4. Native chromatin fractionation, cell-cycle synchronization, mass spectrometry, electron microscopy, FRAP Cell Medium 22817894
2009 CENP-A is rapidly recruited to DNA double-strand breaks along with CENP-N, CENP-T, and CENP-U; the centromere-targeting domain (CATD) of CENP-A is both necessary and sufficient for DSB recruitment; CENP-A accumulation at breaks is enhanced by active NHEJ but is independent of DNA-PKcs, Ligase IV, and H2AX. Multiphoton laser-induced DSBs, I-SceI endonuclease-induced breaks, CENP-A domain mutants, immunofluorescence in human and mouse cells Proceedings of the National Academy of Sciences of the United States of America Medium 19717431
2001 CENP-A is phosphorylated at a serine residue (analogous to H3 Ser10) during mitosis, occurring after pericentric H3 phosphorylation; phosphorylation begins in prophase, peaks in prometaphase, and is lost by telophase, defining CENP-A phosphorylation as a distinct kinetochore-specific mitotic event. Phospho-specific peptide antibodies, ELISA, western blot, immunofluorescence across cell cycle stages Journal of cell science Medium 11171370
2014 Overexpressed CENP-A mislocalizes to non-centromeric chromatin through a heterotypic tetramer containing CenH3-H4 with H3.3-H4, deposited by the H3.3 chaperone DAXX rather than the dedicated chaperone HJURP; ectopic CENP-A occludes CTCF binding and both effects depend on DAXX. Native ChIP-seq, co-immunoprecipitation, siRNA depletion of chaperones in human cells Molecular cell High 24530302
2018 HJURP transiently associates with centromeres during S phase and binds to pre-existing CENP-A; HJURP co-purifies with the MCM2-7 helicase complex and simultaneously binds CENP-A with MCM2, establishing HJURP as an S-phase retention factor required for inheritance of centromeric CENP-A nucleosomes through DNA replication. BioID proximity labeling, co-immunoprecipitation, siRNA depletion, in vitro binding assays Developmental cell High 30293838
2017 CENP-A undergoes α-amino trimethylation by the enzyme NRMT in vivo; loss of this modification reduces CENP-T and CENP-I levels at the centromere and causes lagging chromosomes and spindle pole defects. Mass spectrometry identification of modification, in vivo functional assays with CENP-A N-terminal mutants, immunofluorescence Nature communications Medium 28266506
2022 Cryo-EM structures of the human inner kinetochore CCAN complex bound to a CENP-A nucleosome show CCAN makes edge-on contacts with CENP-A nucleosomes; linker DNA threading through the CENP-LN channel and partial wrapping by CENP-TWSX provide topological entrapment of DNA as a mechanism to withstand spindle forces. Cryo-electron microscopy structure determination of reconstituted CCAN–CENP-A nucleosome complex Science (New York, N.Y.) High 35420891
2011 The CCAN has two distinct roles: (1) recruiting CENP-A to establish the kinetochore (via HJURP, CENP-C, CENP-I, or CENP-C C-terminus) and (2) serving as a structural core to directly recruit kinetochore proteins (Ndc80/CPC) independently of CENP-A (via CENP-T or CENP-C N-terminus). Chromosome engineering with conditional centromere removal, ectopic targeting of individual CCAN proteins, immunofluorescence in DT40 cells The Journal of cell biology High 23277427
2010 Forced reduction of CENP-A triggers premature cellular senescence in human primary fibroblasts in a p53-dependent manner; in p53-deficient cells, CENP-A depletion instead causes aberrant mitosis with chromosome missegregation, revealing a p53-dependent safeguard against centromere defects. shRNA knockdown of CENP-A in human fibroblasts, β-galactosidase senescence assay, chromosome segregation analysis Molecular and cellular biology Medium 20160010
2002 PARP-2 co-immunoprecipitates with CENP-A and CENP-B at mammalian centromeres in a cell-cycle-dependent manner (enriched prometaphase/metaphase, absent by telophase); PARP-2 centromere binding is sequence-independent and occurs only at active centromeres. Co-immunoprecipitation, immunofluorescence on pseudodicentric and neocentromere-containing chromosomes Human molecular genetics Medium 12217960
2015 CENP-B forms a stable complex with the CENP-A nucleosome specifically when the CENP-B box sequence is located at the proximal edge of the nucleosome; the CENP-B DNA-binding domain interacts directly with the CENP-A–H4 complex (but not H3.1–H4); CENP-B binding near CENP-A nucleosomes stabilizes CENP-A on alphoid DNA in human cells. In vitro reconstitution, pulldown assays, in vivo CENP-A stability assay Nucleic acids research High 25916850
2019 CENP-C binding to the CENP-A nucleosome causes two key conformational changes: further exacerbation of loose DNA wrapping via destabilization of the H2A C-terminal tail, and rigidification of the H4 N-terminal tail in a conformation favoring H4K20 monomethylation; CENP-C binds exclusively to CENP-A nucleosomes via an extended hydrophobic interface involving CENP-A V532/V533. Cryo-EM, in vitro binding assays (EMSA, MST), mutagenesis EMBO reports High 31475439
2019 Cryo-EM structure of native-like human CENP-A nucleosome on α-satellite DNA at 2.6 Å resolution reveals the atomic architecture of the CENP-A octameric nucleosome; scFv binds the H2A-H2B acidic patch without perturbing nucleosome structure. Cryo-EM structure determination with scFv stabilization Nature communications High 31127102
2016 The flexible DNA ends of CENP-A nucleosomes (conferred by the short αN helix) prevent histone H1 binding; substituting the CENP-A αN helix with the H3 αN helix rigidifies DNA ends, enables H1 binding, causes delocalization of kinetochore proteins, and produces mitotic and cytokinesis defects in vivo. Cryo-EM, biochemical H1 binding assays, in vivo H3-CENP-A chimera expression with kinetochore localization and mitotic phenotype readout Molecular cell High 27499292
2017 Two HJURP repeats bind concomitantly to the 4:2:2 Mis18α:Mis18β:M18BP1 complex without dissociating it; Mis18α N-terminal tails blockade two identical HJURP-repeat binding sites near the Mis18αβ C-terminal helices; mutation of these sites separates Mis18 from HJURP centromere recruitment. Photo-cross-linking, in vitro binding assays, point mutagenesis, immunofluorescence Nature communications High 31492860
2017 CDK1 phosphorylation at two conserved sites in M18BP1's N-terminal 140 residues destabilizes its binding to the Mis18α:Mis18β hexamer (4:2 stoichiometry), limiting Mis18 complex formation and centromere recruitment of HJURP/CENP-A loading to G1 phase. Biochemical reconstitution, viral 2A co-expression system, phosphomutant analysis, centromere localization assays eLife High 28059702
2018 Aurora A phosphorylates CENP-A at serine 7 at inner centromeres; non-phosphorylatable CENP-A S7A weakens sister chromatid cohesion only under spindle tension, and Aurora A is recruited to centromeres in a Bub1-dependent manner; this modification protects bioriented chromosomes against cohesion fatigue. Phospho-specific antibody, non-phosphorylatable CENP-A mutant expression, Aurora A inhibition/depletion, cohesion fatigue assay Nature communications Medium 29760389
2016 KAT7/HBO1 acetyltransferase interacts with the CENP-A assembly factor M18BP1; KAT7 knockout reduces centromeric CENP-A assembly; tethering KAT7 to ectopic alphoid DNA removes H3K9me3 and stimulates CENP-A assembly by antagonizing Suv39h1-mediated heterochromatin invasion. Co-immunoprecipitation, KO cell line, tethering assay, chromatin immunoprecipitation Developmental cell Medium 27270040
2016 CENP-A K124 is acetylated by p300 at G1/S and switches to monomethylation during early and mid-S phase; acetylation of K124 diminishes CENP-C binding and promotes DNA sliding of nucleosomes; K124 mutation alters CENP-C levels and centromeric replication timing. Mass spectrometry, computational modeling, in vivo K124 acetyl/unacetylatable mutant expression, immunofluorescence Epigenetics & chromatin Medium 28396698
2016 CENP-A ubiquitylation (K124, by CUL4A-RBX1-COPS8) is inherited through cell divisions; pre-existing ubiquitylated CENP-A is necessary for recruitment of newly synthesized CENP-A; inheritance of ubiquitylation requires CENP-A dimerization, as shown by dimerization mutants. In vivo and in vitro dimerization mutant analysis, cell cycle tracking of ubiquitylated CENP-A, immunofluorescence Cell reports Medium 27052173
2020 Spt6 (histone chaperone and transcription elongation factor) directly binds to dCENP-A and prevents loss of old CENP-A nucleosomes during centromeric transcription in both Drosophila and human cells; phosphomimetic dCENP-A residues reduce Spt6 association and CENP-A retention at centromeres. Direct binding assay (Spt6–dCENP-A), phosphomutant CENP-A expression, immunofluorescence in Drosophila and human cells Nature communications Medium 32522980
2024 CENP-A acts as an m6A reader of centromeric RNA (cenRNA): m6A-modified cenRNA stabilizes centromeric localization of CENP-A during S phase; mutations at CENP-A Leu61 and Arg63 abolish this interaction, leading to loss of centromere-bound CENP-A during S phase, compromised centromere integrity, and abnormal chromosome segregation. m6A-seq, CENP-A point mutagenesis, ChIP, chromosome segregation assays in cancer cells Cell High 39305902
2019 Centromeric tri-nucleosome cryo-EM structures show that H3-CENP-A-H3 tri-nucleosomes adopt an untwisted architecture with outward-facing linker DNA between nucleosomes, distinct from canonical H3-H3-H3 tri-nucleosomes; this configuration may expose the CENP-A nucleosome in condensed chromatin for centromeric protein access. Cryo-EM structure of reconstituted tri-nucleosomes containing central CENP-A nucleosome Structure (London, England : 1993) High 31711756
2015 Both the N-terminal tail (small portion) and the centromere-targeting domain (CATD) of CENP-A are required for initial recruitment of CENP-C and CENP-T during centromere establishment; these requirements differ from those for maintaining centromere identity. LacI-LacO tethering of H3-CENP-A chimeras, immunofluorescence readout of CENP-C and CENP-T recruitment The Journal of cell biology Medium 25713413
2013 Natively assembled human CENP-A nucleosomes are octameric throughout the cell cycle, containing CENP-A dimers along with H2B and H4; CENP-A associated with HJURP can exist as monomer or dimer, indicating possible assembly intermediates. TIRF-coupled photobleaching copy-number counting of single nucleosomes from cultured cells Current biology : CB Medium 23623556
2015 CRL4(RBBP7) E3 ubiquitin ligase complex (CUL4-DDB1-RBBP7) is required for centromeric loading of CENP-A during G1 but does not influence CENP-A maintenance or pre-nucleosomal CENP-A levels; RBBP7 also binds and stabilizes soluble CENP-A. siRNA depletion of CRL4 components, quantitative imaging of CENP-A loading, co-immunoprecipitation Journal of cell science Medium 25795299

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 The human CENP-A centromeric nucleosome-associated complex. Nature cell biology 592 16622419
2000 Early disruption of centromeric chromatin organization in centromere protein A (Cenpa) null mice. Proceedings of the National Academy of Sciences of the United States of America 328 10655499
2002 Centromeric retroelements and satellites interact with maize kinetochore protein CENH3. The Plant cell 296 12417704
2011 Epigenetic centromere propagation and the nature of CENP-a nucleosomes. Cell 282 21335232
2007 Nonhistone Scm3 and histones CenH3-H4 assemble the core of centromere-specific nucleosomes. Cell 244 17574026
2008 Heterochromatin and RNAi are required to establish CENP-A chromatin at centromeres. Science (New York, N.Y.) 234 18174443
2014 Mislocalization of the centromeric histone variant CenH3/CENP-A in human cells depends on the chaperone DAXX. Molecular cell 211 24530302
2011 CENP-C recruits M18BP1 to centromeres to promote CENP-A chromatin assembly. The Journal of cell biology 187 21911481
2012 The CCAN recruits CENP-A to the centromere and forms the structural core for kinetochore assembly. The Journal of cell biology 182 23277427
2014 Recurrent loss of CenH3 is associated with independent transitions to holocentricity in insects. eLife 169 25247700
2014 Polo-like kinase 1 licenses CENP-A deposition at centromeres. Cell 151 25036634
2011 Structure of a CENP-A-histone H4 heterodimer in complex with chaperone HJURP. Genes & development 151 21478274
2009 Double-strand DNA breaks recruit the centromeric histone CENP-A. Proceedings of the National Academy of Sciences of the United States of America 130 19717431
2015 CENP-A nucleosomes localize to transcription factor hotspots and subtelomeric sites in human cancer cells. Epigenetics & chromatin 122 25788983
2016 CENH3-GFP: a visual marker for gametophytic and somatic ploidy determination in Arabidopsis thaliana. BMC plant biology 116 26728271
2014 CAL1 is the Drosophila CENP-A assembly factor. The Journal of cell biology 115 24469636
2012 Cell-cycle-dependent structural transitions in the human CENP-A nucleosome in vivo. Cell 115 22817894
2008 The histone variant CENP-A and centromere specification. Current opinion in cell biology 114 18226513
2015 Naturally occurring differences in CENH3 affect chromosome segregation in zygotic mitosis of hybrids. PLoS genetics 111 25622028
2018 Centromere transcription allows CENP-A to transit from chromatin association to stable incorporation. The Journal of cell biology 105 29626011
2015 Point mutation impairs centromeric CENH3 loading and induces haploid plants. Proceedings of the National Academy of Sciences of the United States of America 99 26294252
2011 Xenopus HJURP and condensin II are required for CENP-A assembly. The Journal of cell biology 93 21321101
2022 Structure of the human inner kinetochore bound to a centromeric CENP-A nucleosome. Science (New York, N.Y.) 91 35420891
2021 Haploid induction by a maize cenh3 null mutant. Science advances 91 33523932
2014 Dynamic phosphorylation of CENP-A at Ser68 orchestrates its cell-cycle-dependent deposition at centromeres. Developmental cell 90 25556658
2010 CENP-A reduction induces a p53-dependent cellular senescence response to protect cells from executing defective mitoses. Molecular and cellular biology 90 20160010
2001 Differential regulation of CENP-A and histone H3 phosphorylation in G2/M. Journal of cell science 90 11171370
2014 A cooperative mechanism drives budding yeast kinetochore assembly downstream of CENP-A. The Journal of cell biology 88 25135934
2012 CENP-A: the key player behind centromere identity, propagation, and kinetochore assembly. Chromosoma 88 23095988
2015 Both tails and the centromere targeting domain of CENP-A are required for centromere establishment. The Journal of cell biology 86 25713413
2016 Maternal Haploids Are Preferentially Induced by CENH3-tailswap Transgenic Complementation in Maize. Frontiers in plant science 83 27066050
2016 The Flexible Ends of CENP-A Nucleosome Are Required for Mitotic Fidelity. Molecular cell 82 27499292
2011 Knockdown of CENH3 in Arabidopsis reduces mitotic divisions and causes sterility by disturbed meiotic chromosome segregation. The Plant journal : for cell and molecular biology 81 21635586
2018 Inheritance of CENP-A Nucleosomes during DNA Replication Requires HJURP. Developmental cell 80 30293838
2016 KAT7/HBO1/MYST2 Regulates CENP-A Chromatin Assembly by Antagonizing Suv39h1-Mediated Centromere Inactivation. Developmental cell 79 27270040
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 79 12217960
2020 The centromere comes into focus: from CENP-A nucleosomes to kinetochore connections with the spindle. Open biology 78 32516549
2017 CDK-regulated dimerization of M18BP1 on a Mis18 hexamer is necessary for CENP-A loading. eLife 72 28059702
2020 A variety of changes, including CRISPR/Cas9-mediated deletions, in CENH3 lead to haploid induction on outcrossing. Plant biotechnology journal 66 32096293
2012 Putting CENP-A in its place. Cellular and molecular life sciences : CMLS 66 22729156
2019 Atomic resolution cryo-EM structure of a native-like CENP-A nucleosome aided by an antibody fragment. Nature communications 64 31127102
2017 α-amino trimethylation of CENP-A by NRMT is required for full recruitment of the centromere. Nature communications 61 28266506
2019 Quiescent Cells Actively Replenish CENP-A Nucleosomes to Maintain Centromere Identity and Proliferative Potential. Developmental cell 60 31422918
2005 Characterization of CENH3 and centromere-associated DNA sequences in sugarcane. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 60 15861308
2019 CENP-C unwraps the human CENP-A nucleosome through the H2A C-terminal tail. EMBO reports 56 31475439
2017 Molecular basis for Cdk1-regulated timing of Mis18 complex assembly and CENP-A deposition. EMBO reports 56 28377371
2020 The role of the histone H3 variant CENPA in prostate cancer. The Journal of biological chemistry 53 32371391
2017 Centromere location in Arabidopsis is unaltered by extreme divergence in CENH3 protein sequence. Genome research 53 28223399
2020 CenH3-Independent Kinetochore Assembly in Lepidoptera Requires CCAN, Including CENP-T. Current biology : CB 52 32032508
2019 Mechanism of centromere recruitment of the CENP-A chaperone HJURP and its implications for centromere licensing. Nature communications 52 31492860
2015 Stable complex formation of CENP-B with the CENP-A nucleosome. Nucleic acids research 52 25916850
2012 Methylation of CenH3 arginine 37 regulates kinetochore integrity and chromosome segregation. Proceedings of the National Academy of Sciences of the United States of America 52 22615363
2019 Cryo-EM Structures of Centromeric Tri-nucleosomes Containing a Central CENP-A Nucleosome. Structure (London, England : 1993) 50 31711756
2017 Molecular basis of CENP-C association with the CENP-A nucleosome at yeast centromeres. Genes & development 47 29074736
2014 Characterization of two CENH3 genes and their roles in wheat evolution. The New phytologist 47 25557089
2014 Ectopic centromere nucleation by CENP--a in fission yeast. Genetics 46 25298518
2005 Two distinct pathways responsible for the loading of CENP-A to centromeres in the fission yeast cell cycle. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 46 15897182
2018 HJURP antagonizes CENP-A mislocalization driven by the H3.3 chaperones HIRA and DAXX. PloS one 45 30365520
2009 Lineage-specific adaptive evolution of the centromeric protein CENH3 in diploid and allotetraploid Oryza species. Molecular biology and evolution 43 19741004
2013 Octameric CENP-A nucleosomes are present at human centromeres throughout the cell cycle. Current biology : CB 42 23623556
2020 Formation of the CenH3-Deficient Holocentromere in Lepidoptera Avoids Active Chromatin. Current biology : CB 41 33125865
2018 Posttranslational modifications of CENP-A: marks of distinction. Chromosoma 41 29569072
2019 The H3 histone chaperone NASPSIM3 escorts CenH3 in Arabidopsis. The Plant journal : for cell and molecular biology 39 31463991
2016 Differential Chromosomal Localization of Centromeric Histone CENP-A Contributes to Nematode Programmed DNA Elimination. Cell reports 39 27545882
2017 CENP-A chromatin disassembly in stressed and senescent murine cells. Scientific reports 38 28186195
2016 No longer a nuisance: long non-coding RNAs join CENP-A in epigenetic centromere regulation. Cellular and molecular life sciences : CMLS 37 26748759
2016 Regulation of Budding Yeast CENP-A levels Prevents Misincorporation at Promoter Nucleosomes and Transcriptional Defects. PLoS genetics 37 26982580
2016 CENPT bridges adjacent CENPA nucleosomes on young human α-satellite dimers. Genome research 37 27384170
2016 Inheritance of the CENP-A chromatin domain is spatially and temporally constrained at human centromeres. Epigenetics & chromatin 35 27252782
2013 Esperanto for histones: CENP-A, not CenH3, is the centromeric histone H3 variant. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 35 23580138
2020 Spt6 is a maintenance factor for centromeric CENP-A. Nature communications 34 32522980
2018 Nanoscale dynamics of centromere nucleosomes and the critical roles of CENP-A. Nucleic acids research 34 29040671
2011 The E2F transcription factor family regulates CENH3 expression in Arabidopsis thaliana. The Plant journal : for cell and molecular biology 34 21771121
2022 CENP-A Regulation and Cancer. Frontiers in cell and developmental biology 33 35721491
2017 Internal modifications in the CENP-A nucleosome modulate centromeric dynamics. Epigenetics & chromatin 32 28396698
2009 CENPA a genomic marker for centromere activity and human diseases. Current genomics 32 20119530
2013 Hypermorphic expression of centromeric retroelement-encoded small RNAs impairs CENP-A loading. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 31 23392618
2000 Fine-specificity of the anti-CENP-A B-cell autoimmune response. Journal of molecular medicine (Berlin, Germany) 30 11097115
2024 m6A-modified cenRNA stabilizes CENPA to ensure centromere integrity in cancer cells. Cell 28 39305902
2018 Aurora A-dependent CENP-A phosphorylation at inner centromeres protects bioriented chromosomes against cohesion fatigue. Nature communications 28 29760389
2010 Recognition of A. thaliana centromeres by heterologous CENH3 requires high similarity to the endogenous protein. Plant molecular biology 28 21190064
2021 High-throughput AFM analysis reveals unwrapping pathways of H3 and CENP-A nucleosomes. Nanoscale 27 33683227
2020 Stable inheritance of CENP-A chromatin: Inner strength versus dynamic control. The Journal of cell biology 27 32931551
2016 CENP-A Ubiquitylation Is Inherited through Dimerization between Cell Divisions. Cell reports 27 27052173
2009 Epigenetic specification of centromeres by CENP-A. Experimental cell research 27 19660450
2020 Targeted De Novo Centromere Formation in Drosophila Reveals Plasticity and Maintenance Potential of CENP-A Chromatin. Developmental cell 26 32049040
2020 Structural basis for centromere maintenance by Drosophila CENP-A chaperone CAL1. The EMBO journal 26 32134144
2012 Cell cycle-dependent deposition of CENP-A requires the Dos1/2-Cdc20 complex. Proceedings of the National Academy of Sciences of the United States of America 26 23267073
2025 Centrophilic retrotransposon integration via CENH3 chromatin in Arabidopsis. Nature 25 39743586
1999 CENP-A associated complex satellite DNA in the kinetochore of the Indian muntjac. Chromosoma 25 10591996
2021 Centromere Protein A (CENPA) Regulates Metabolic Reprogramming in the Colon Cancer Cells by Transcriptionally Activating Karyopherin Subunit Alpha 2 (KPNA2). The American journal of pathology 24 34508688
2019 The deposition of CENH3 in maize is stringently regulated. The Plant journal : for cell and molecular biology 24 31713923
2015 CRL4(RBBP7) is required for efficient CENP-A deposition at centromeres. Journal of cell science 24 25795299
2012 Replicating centromeric chromatin: spatial and temporal control of CENP-A assembly. Experimental cell research 24 22561213
2011 Deposition, turnover, and release of CENH3 at Arabidopsis centromeres. Chromosoma 24 21842230
2020 Unequal contribution of two paralogous CENH3 variants in cowpea centromere function. Communications biology 23 33319863
2012 Comparison between the CENP-A and histone H3 structures in nucleosomes. Nucleus (Austin, Tex.) 23 22127263
2014 Short hairpin RNA-mediated down-regulation of CENP-A attenuates the aggressive phenotype of lung adenocarcinoma cells. Cellular oncology (Dordrecht, Netherlands) 21 25228009
2019 In vitro BioID: mapping the CENP-A microenvironment with high temporal and spatial resolution. Molecular biology of the cell 20 30892990
2013 CENP-A is essential for cardiac progenitor cell proliferation. Cell cycle (Georgetown, Tex.) 20 24362315