id: Q13112
gene_symbol: CHAF1B
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  CHAF1B (p60, CAF-1 subunit B) is the WD40-repeat medium subunit of Chromatin
  Assembly Factor 1 (CAF-1), a heterotrimeric histone H3-H4 chaperone composed of
  CHAF1A (p150), CHAF1B (p60), and RBBP4 (p48). Within CAF-1, p60 bridges the large
  subunit CHAF1A and the histone-binding subunit RBBP4, and the direct p150-p60
  interaction is required for CAF-1-mediated nucleosome assembly. CAF-1 performs the
  first step of nucleosome assembly by depositing newly synthesized histones H3.1-H4
  onto DNA in a replication-coupled (DNA-synthesis-dependent) manner, and it is also
  recruited to chromatin undergoing DNA repair. CHAF1B is built from an N-terminal
  seven-bladed WD40 beta-propeller and a C-terminal disordered region that is heavily
  phosphorylated in a cell-cycle-dependent fashion. The active complex resides in the
  nucleus, where it concentrates at DNA replication foci during S phase; during mitosis
  the p60 subunit is hyperphosphorylated, CAF-1 is inactivated, and p60 is displaced
  into the cytoplasm. The gene maps to chromosome 21q22.
existing_annotations:
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Phylogenetically-inferred nuclear localization. The active CAF-1 complex,
      including CHAF1B, is nuclear and concentrates at DNA replication foci during
      S phase, so this is the correct primary site of action.
    action: ACCEPT
    reason: >-
      Nuclear localization is well supported experimentally for human CAF-1 in
      interphase, where p150 and p60 are bound to the nucleus and concentrate at
      sites of intranuclear DNA replication during S phase.
    supported_by:
    - reference_id: PMID:9614144
      supporting_text: >-
        In interphase, p150 and p60 are bound to the nucleus, but they
        predominantly dissociate from chromatin during mitosis. During S phase,
        p150 and p60 are concentrated at sites of intranuclear DNA replication.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Electronic transfer of nuclear localization from the UniProt subcellular
      location vocabulary. Redundant with the IBA/NAS nucleus annotations but
      correct; retained as non-core duplicate of the primary nuclear assignment.
    action: KEEP_AS_NON_CORE
    reason: >-
      Correct localization but a redundant electronic duplicate of the
      experimentally supported nucleus annotation.
    supported_by:
    - reference_id: file:human/CHAF1B/CHAF1B-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9614144}.'
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Electronic transfer of cytoplasmic localization. CHAF1B is cytoplasmic only
      as the inactive, hyperphosphorylated M-phase form displaced from chromatin;
      this is a secondary, regulated location, not the site of CAF-1 activity.
    action: KEEP_AS_NON_CORE
    reason: >-
      Cytoplasmic localization is real but corresponds to the inactive M-phase
      pool of p60 displaced into the cytosol, not the active nuclear function.
    supported_by:
    - reference_id: file:human/CHAF1B/CHAF1B-uniprot.txt
      supporting_text: >-
        Cytoplasm {ECO:0000269|PubMed:9614144}. Note=DNA replication foci.
        Cytoplasmic in M phase.
- term:
    id: GO:0006335
    label: DNA replication-dependent chromatin assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: >-
      InterPro2GO electronic transfer of the core CAF-1 process. Correct and
      consistent with the direct experimental annotations of the same term, but
      redundant with them.
    action: KEEP_AS_NON_CORE
    reason: >-
      Electronic InterPro2GO duplicate of the experimentally supported core
      process term; correct but redundant.
    supported_by:
    - reference_id: PMID:8858152
      supporting_text: >-
        copurifies with a chromatin assembly complex (CAC), which contains the
        three subunits of CAF-1 (p150, p60, p48) and H3 and H4, and promotes DNA
        replication-dependent chromatin assembly.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16980972
  qualifier: enables
  review:
    summary: >-
      Bare protein binding capturing the CAF-1 p60 interaction with ASF1a/ASF1b.
      Although this is a biologically meaningful histone-chaperone hand-off, the
      GO term itself is uninformative as a molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Per curation guidelines, bare 'protein binding' is uninformative. The
      underlying ASF1-p60 interaction is better represented by histone chaperone
      activity and complex membership terms.
    supported_by:
    - reference_id: PMID:16980972
      supporting_text: >-
        CAF-1 p60 also uses B domain-like motifs for binding to ASF1a, thereby
        competing with HIRA.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24981860
  qualifier: enables
  review:
    summary: >-
      Bare protein binding from a high-throughput chromatin-related interactome
      study (interactor ASF1A). Uninformative as a molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Generic 'protein binding' from a large-scale interaction map; provides no
      specific molecular function information.
    supported_by:
    - reference_id: PMID:24981860
      supporting_text: >-
        Human-chromatin-related protein interactions identify a demethylase
        complex required for chromosome segregation.
      reference_section_type: TITLE
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27705803
  qualifier: enables
  review:
    summary: >-
      Bare protein binding from a high-throughput Polycomb complexome AP-MS map
      (interactor ASF1B). Uninformative as a molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Generic 'protein binding' from a large-scale interaction map; provides no
      specific molecular function information.
    supported_by:
    - reference_id: PMID:27705803
      supporting_text: A High-Density Map for Navigating the Human Polycomb Complexome.
      reference_section_type: TITLE
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: >-
      Bare protein binding from the BioPlex high-throughput AP-MS interactome
      (interactor ASF1B). Uninformative as a molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Generic 'protein binding' from a large-scale interaction map; provides no
      specific molecular function information.
    supported_by:
    - reference_id: PMID:28514442
      supporting_text: >-
        Architecture of the human interactome defines protein communities and
        disease networks.
      reference_section_type: TITLE
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: >-
      Bare protein binding from the BioPlex dual proteome-scale interactome
      (interactor ASF1B). Uninformative as a molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Generic 'protein binding' from a large-scale interaction map; provides no
      specific molecular function information.
    supported_by:
    - reference_id: PMID:33961781
      supporting_text: >-
        Dual proteome-scale networks reveal cell-specific remodeling of the human
        interactome.
      reference_section_type: TITLE
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: >-
      Bare protein binding from a high-throughput multimodal cell-map study
      (interactor ASF1B). Uninformative as a molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Generic 'protein binding' from a large-scale interaction map; provides no
      specific molecular function information.
    supported_by:
    - reference_id: PMID:40205054
      supporting_text: >-
        Multimodal cell maps as a foundation for structural and functional
        genomics.
      reference_section_type: TITLE
- term:
    id: GO:0006335
    label: DNA replication-dependent chromatin assembly
  evidence_type: IDA
  original_reference_id: PMID:14718166
  qualifier: involved_in
  review:
    summary: >-
      Direct evidence that CAF-1 (containing CHAF1B) mediates the
      DNA-synthesis-dependent nucleosome assembly pathway via histone H3.1-H4
      deposition. This is the core biological process of the gene.
    action: ACCEPT
    reason: >-
      CHAF1B is an essential subunit of the CAF-1 complex that mediates
      replication-coupled (DNA-synthesis-dependent) nucleosome assembly, the gene's
      defining process.
    supported_by:
    - reference_id: PMID:14718166
      supporting_text: >-
        The H3.1 and H3.3 complexes contain distinct histone chaperones, CAF-1 and
        HIRA, that we show are necessary to mediate DNA-synthesis-dependent and
        -independent nucleosome assembly, respectively.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: >-
      Immunofluorescence (HPA) nucleoplasmic localization, consistent with the
      nuclear site of CAF-1 action. Retained as a non-core refinement of the
      primary nucleus annotation.
    action: KEEP_AS_NON_CORE
    reason: >-
      Consistent nuclear/nucleoplasmic localization; a more granular but
      non-core refinement of the core nucleus assignment.
    supported_by:
    - reference_id: PMID:9614144
      supporting_text: In interphase, p150 and p60 are bound to the nucleus.
      reference_section_type: ABSTRACT
- term:
    id: GO:0000785
    label: chromatin
  evidence_type: IDA
  original_reference_id: PMID:9614144
  qualifier: located_in
  review:
    summary: >-
      CAF-1 binds chromatin and concentrates at replication foci during S phase,
      dissociating during mitosis. Chromatin localization is consistent with the
      gene's role in chromatin assembly on replicating DNA.
    action: ACCEPT
    reason: >-
      CHAF1B/CAF-1 acts directly on chromatin at sites of DNA replication;
      chromatin localization is well supported and integral to its function.
    supported_by:
    - reference_id: PMID:9614144
      supporting_text: >-
        In interphase, p150 and p60 are bound to the nucleus, but they
        predominantly dissociate from chromatin during mitosis. During S phase,
        p150 and p60 are concentrated at sites of intranuclear DNA replication.
      reference_section_type: ABSTRACT
- term:
    id: GO:0006335
    label: DNA replication-dependent chromatin assembly
  evidence_type: IDA
  original_reference_id: PMID:9614144
  qualifier: involved_in
  review:
    summary: >-
      Direct evidence that human CAF-1 (including p60) mediates nucleosome
      assembly coupled to DNA synthesis. Core process of the gene.
    action: ACCEPT
    reason: >-
      Replication-coupled nucleosome assembly is the defining function of CAF-1
      and its CHAF1B subunit.
    supported_by:
    - reference_id: PMID:9614144
      supporting_text: >-
        Human CAF-1 efficiently mediates nucleosome assembly during complementary
        DNA strand synthesis in G1, S, and G2 phase cytosolic extracts.
      reference_section_type: ABSTRACT
- term:
    id: GO:0033186
    label: CAF-1 complex
  evidence_type: IPI
  original_reference_id: PMID:9614144
  qualifier: part_of
  review:
    summary: >-
      CHAF1B (p60) is a core subunit of the CAF-1 complex together with CHAF1A
      (p150) and RBBP4 (p48). This is the defining complex membership of the gene.
    action: ACCEPT
    reason: >-
      CHAF1B is one of the three constitutive subunits of CAF-1; complex
      membership is central to its identity and function.
    supported_by:
    - reference_id: PMID:9614144
      supporting_text: >-
        All three subunits of human CAF-1 (p150, p60, and p48) are present during
        the entire cell cycle.
      reference_section_type: ABSTRACT
- term:
    id: GO:0006335
    label: DNA replication-dependent chromatin assembly
  evidence_type: IDA
  original_reference_id: PMID:8858152
  qualifier: involved_in
  review:
    summary: >-
      The chromatin assembly complex containing the three CAF-1 subunits and
      histones H3/H4 promotes DNA replication-dependent chromatin assembly. Core
      process.
    action: ACCEPT
    reason: >-
      Direct biochemical evidence that the CAF-1-containing complex promotes
      replication-dependent chromatin assembly, the gene's core process.
    supported_by:
    - reference_id: PMID:8858152
      supporting_text: >-
        copurifies with a chromatin assembly complex (CAC), which contains the
        three subunits of CAF-1 (p150, p60, p48) and H3 and H4, and promotes DNA
        replication-dependent chromatin assembly.
      reference_section_type: ABSTRACT
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: IDA
  original_reference_id: PMID:14718166
  qualifier: part_of
  review:
    summary: >-
      Generic complex membership. CHAF1B is part of the specific CAF-1 complex
      (GO:0033186), so the root-level protein-containing complex term is an
      over-general annotation.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The specific CAF-1 complex term is annotated and is far more informative;
      the generic protein-containing complex term adds no information.
    supported_by:
    - reference_id: PMID:14718166
      supporting_text: >-
        these complexes possess one molecule each of H3.1/H3.3 and H4, suggesting
        that histones H3 and H4 exist as dimeric units that are important
        intermediates in nucleosome formation.
      reference_section_type: ABSTRACT
- term:
    id: GO:0000785
    label: chromatin
  evidence_type: IDA
  original_reference_id: PMID:14718166
  qualifier: located_in
  review:
    summary: >-
      CAF-1 acts on chromatin during replication-coupled H3.1-H4 deposition;
      chromatin localization is consistent with the gene's nucleosome assembly
      role.
    action: ACCEPT
    reason: >-
      Chromatin is the direct substrate location for CAF-1-mediated nucleosome
      assembly; well supported and functionally integral.
    supported_by:
    - reference_id: PMID:14718166
      supporting_text: >-
        The H3.1 and H3.3 complexes contain distinct histone chaperones, CAF-1 and
        HIRA, that we show are necessary to mediate DNA-synthesis-dependent and
        -independent nucleosome assembly, respectively.
      reference_section_type: ABSTRACT
- term:
    id: GO:0033186
    label: CAF-1 complex
  evidence_type: IDA
  original_reference_id: PMID:8858152
  qualifier: part_of
  review:
    summary: >-
      CHAF1B is a constitutive subunit of the CAF-1 complex (with CHAF1A and
      RBBP4). Defining complex membership.
    action: ACCEPT
    reason: >-
      Core CAF-1 complex membership, biochemically demonstrated in the chromatin
      assembly complex containing all three subunits.
    supported_by:
    - reference_id: PMID:8858152
      supporting_text: >-
        a chromatin assembly complex (CAC), which contains the three subunits of
        CAF-1 (p150, p60, p48) and H3 and H4.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: HDA
  original_reference_id: PMID:16780588
  qualifier: colocalizes_with
  review:
    summary: >-
      High-throughput colocalization with the cytosol. CHAF1B is cytosolic only as
      the inactive M-phase form translocated out of the nucleus during cell
      division; this is a regulated secondary location, not the site of activity.
    action: KEEP_AS_NON_CORE
    reason: >-
      The cytosolic pool corresponds to the inactive M-phase form of p60; it is a
      genuine but non-core, cell-cycle-restricted location.
    supported_by:
    - reference_id: PMID:16780588
      supporting_text: >-
        The chromatin assembly factor I p60 subunit (CHAF1B) protein translocated
        from the nucleus into the cytoplasm during cell division.
      reference_section_type: RESULTS
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: HDA
  original_reference_id: PMID:16780588
  qualifier: colocalizes_with
  review:
    summary: >-
      High-throughput colocalization with the nucleoplasm, consistent with the
      nuclear site of CAF-1 action at interphase.
    action: KEEP_AS_NON_CORE
    reason: >-
      Nucleoplasmic localization is consistent with the core nuclear function but
      is a non-core refinement supported by high-throughput data.
    supported_by:
    - reference_id: PMID:16780588
      supporting_text: >-
        most of the CHAF1B protein localizing in the nucleus at interphase, where
        it is involved in chromatin assembly and DNA replication.
      reference_section_type: RESULTS
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: NAS
  original_reference_id: PMID:9614144
  qualifier: located_in
  review:
    summary: >-
      Nuclear localization of CAF-1/p60 in interphase, where the complex performs
      replication-coupled chromatin assembly. Core localization.
    action: ACCEPT
    reason: >-
      The active CAF-1 complex including CHAF1B is nuclear; this is the primary
      site of its function.
    supported_by:
    - reference_id: PMID:9614144
      supporting_text: In interphase, p150 and p60 are bound to the nucleus.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: NAS
  original_reference_id: PMID:9614144
  qualifier: located_in
  review:
    summary: >-
      Cytoplasmic localization corresponds to the inactive, hyperphosphorylated
      M-phase form of p60 displaced from chromatin; a regulated secondary location.
    action: KEEP_AS_NON_CORE
    reason: >-
      Real but non-core; reflects the inactive mitotic pool rather than the active
      nuclear function.
    supported_by:
    - reference_id: PMID:9614144
      supporting_text: >-
        In mitosis, the p60 subunit of inactive CAF-1 is hyperphosphorylated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0042393
    label: histone binding
  evidence_type: NAS
  original_reference_id: PMID:7600578
  qualifier: enables
  review:
    summary: >-
      CAF-1 p150/p60 form complexes with newly synthesized histones H3 and
      acetylated H4, and p60 binds histones H3.1/H3.2/H3.1t. Histone binding is a
      core molecular function of this histone chaperone subunit. Cryo-EM structural
      work (Liu et al. 2023, Science) specifically identifies p60/CHAF1B as the
      principal H3-H4-binding subunit of human CAF-1, contacting H4 through its
      ventral beta-propeller surface and engaging a partially unfolded H3 region;
      this is direct, subunit-specific structural support for histone binding by
      CHAF1B itself rather than only by the holo-complex.
    action: ACCEPT
    reason: >-
      CHAF1B directly contacts histones in the CAF-1 complex (newly synthesized
      H3-H4; H3.1/H3.2/H3.1t), supporting histone binding as a core MF. The
      falcon deep-research report (summarizing Liu et al. 2023 cryo-EM) adds
      subunit-resolved structural evidence that p60 is the principal H3-H4-binding
      component and is required for CAF-1 histone binding, reinforcing this as a
      direct molecular function of CHAF1B.
    supported_by:
    - reference_id: PMID:7600578
      supporting_text: >-
        p150 and p60 form complexes with newly synthesized histones H3 and
        acetylated H4 in human cell extracts.
      reference_section_type: ABSTRACT
    - reference_id: file:human/CHAF1B/CHAF1B-uniprot.txt
      supporting_text: Interacts with histones H3.1, H3.2 and H3.1t (PubMed:33857403).
    - reference_id: file:human/CHAF1B/CHAF1B-deep-research-falcon.md
      supporting_text: >-
        The primary molecular function of CHAF1B is to serve as the principal
        histone H3-H4 binding subunit within the CAF-1 complex.
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: TAS
  original_reference_id: PMID:7600578
  qualifier: enables
  review:
    summary: >-
      Chromatin binding is consistent with CAF-1 acting on replicating chromatin,
      but it is a generic molecular function relative to the more informative
      histone chaperone / histone binding activities of CHAF1B.
    action: KEEP_AS_NON_CORE
    reason: >-
      Supported but generic; histone binding and histone chaperone activity are
      more informative descriptors of the molecular function.
    supported_by:
    - reference_id: PMID:9614144
      supporting_text: >-
        During S phase, p150 and p60 are concentrated at sites of intranuclear DNA
        replication.
      reference_section_type: ABSTRACT
- term:
    id: GO:0140713
    label: histone chaperone activity
  evidence_type: IC
  original_reference_id: file:human/CHAF1B/CHAF1B-uniprot.txt
  qualifier: enables
  review:
    summary: Proposed annotation not present in the current GOA for CHAF1B.
    action: NEW
    reason: >-
      CHAF1B is a subunit of the CAF-1 histone H3-H4 chaperone and directly binds
      newly synthesized histones H3-H4 (and H3.1/H3.2/H3.1t). The molecular function
      of the complex is histone chaperone activity, which is not currently captured
      in the CHAF1B GOA and would be more informative than the existing bare protein
      binding annotations. Cryo-EM structural work (Liu et al. 2023) shows p60 is
      not merely a passive scaffold but is required for CAF-1 histone binding and
      nucleosome assembly activity, supporting a subunit-level histone chaperone
      activity annotation.
    supported_by:
    - reference_id: file:human/CHAF1B/CHAF1B-uniprot.txt
      supporting_text: >-
        Acts as a component of the histone chaperone complex chromatin assembly
        factor 1 (CAF-1), which assembles histone octamers onto DNA during
        replication and repair.
    - reference_id: file:human/CHAF1B/CHAF1B-deep-research-falcon.md
      supporting_text: >-
        CHAF1B directly binds H3-H4 and is absolutely required for CAF-1's
        nucleosome assembly activity
core_functions:
- description: >-
    CHAF1B is the WD40 medium subunit (p60) of the CAF-1 histone H3-H4 chaperone,
    binding newly synthesized histones H3.1-H4 and acting as a histone chaperone
    within the complex.
  molecular_function:
    id: GO:0140713
    label: histone chaperone activity
  supported_by:
  - reference_id: PMID:7600578
    supporting_text: >-
      p150 and p60 form complexes with newly synthesized histones H3 and acetylated
      H4 in human cell extracts.
    reference_section_type: ABSTRACT
  - reference_id: file:human/CHAF1B/CHAF1B-deep-research-falcon.md
    supporting_text: >-
      The p60 subunit binds one histone H3-H4 heterodimer mainly through its ventral
      surface area, which is enriched with negatively charged residues along with
      several tyrosine and phenylalanine residues
- description: >-
    As a subunit of CAF-1, CHAF1B mediates the first step of nucleosome assembly,
    depositing newly synthesized H3.1-H4 onto DNA in a replication- and
    repair-coupled manner.
  directly_involved_in:
  - id: GO:0006335
    label: DNA replication-dependent chromatin assembly
  in_complex:
    id: GO:0033186
    label: CAF-1 complex
  locations:
  - id: GO:0005634
    label: nucleus
  - id: GO:0000785
    label: chromatin
  supported_by:
  - reference_id: PMID:8858152
    supporting_text: >-
      a chromatin assembly complex (CAC), which contains the three subunits of
      CAF-1 (p150, p60, p48) and H3 and H4, and promotes DNA replication-dependent
      chromatin assembly.
    reference_section_type: ABSTRACT
- description: >-
    CHAF1B bridges the large subunit CHAF1A (p150) and the histone-binding subunit
    RBBP4 (p48); the direct CHAF1A-CHAF1B interaction is required for CAF-1-mediated
    nucleosome assembly.
  molecular_function:
    id: GO:0042393
    label: histone binding
  supported_by:
  - reference_id: PMID:7600578
    supporting_text: >-
      p150 and p60 directly interact and are both required for DNA
      replication-dependent assembly of nucleosomes. Deletion of the p60-binding
      domain from the p150 protein prevents chromatin assembly.
    reference_section_type: ABSTRACT
proposed_new_terms: []
suggested_questions:
- question: >-
    Is CHAF1B's histone-chaperone activity exerted only as part of the CAF-1
    complex, or does the isolated p60 subunit have an autonomous histone-binding /
    chaperone role that warrants a gene-level molecular-function annotation?
  experts:
  - Kaufman PD
  - Almouzni G
- question: >-
    Does cell-cycle-dependent phosphorylation of the C-terminal disordered region
    of CHAF1B directly regulate CAF-1 assembly activity and its nuclear-cytoplasmic
    partitioning?
  experts:
  - Marheineke K
  - Krude T
suggested_experiments:
- hypothesis: >-
    CHAF1B is required for replication-coupled H3.1-H4 deposition and its loss
    impairs nucleosome assembly genome-wide during S phase.
  description: >-
    Acute degradation (e.g., auxin-inducible degron) of CHAF1B in human cells
    followed by SCAR-seq / nascent-chromatin capture to measure replication-coupled
    new-histone deposition and parental-histone recycling.
  experiment_type: replication-coupled nucleosome assembly assay
- hypothesis: >-
    Mitotic hyperphosphorylation of the CHAF1B C-terminal tail inactivates CAF-1 and
    drives its cytoplasmic relocalization.
  description: >-
    Generate phospho-null and phospho-mimetic mutants of the mapped CHAF1B
    phosphosites and assay CAF-1 nucleosome assembly activity, complex integrity,
    and subcellular localization across the cell cycle.
  experiment_type: phosphomutant functional and localization assay
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: PMID:14718166
  title: Histone H3.1 and H3.3 complexes mediate nucleosome assembly pathways dependent
    or independent of DNA synthesis.
  findings:
  - statement: >-
      The H3.1 deposition machinery is the CAF-1 histone chaperone, which mediates
      DNA-synthesis-dependent (replication-coupled) nucleosome assembly.
    supporting_text: >-
      The H3.1 and H3.3 complexes contain distinct histone chaperones, CAF-1 and
      HIRA, that we show are necessary to mediate DNA-synthesis-dependent and
      -independent nucleosome assembly, respectively.
    reference_section_type: ABSTRACT
    full_text_unavailable: true
- id: PMID:16780588
  title: Cell array-based intracellular localization screening reveals novel functional
    features of human chromosome 21 proteins.
  findings:
  - statement: >-
      CHAF1B is nuclear at interphase (chromatin assembly / DNA replication) and
      translocates to the cytoplasm during cell division.
    supporting_text: >-
      The chromatin assembly factor I p60 subunit (CHAF1B) protein translocated from
      the nucleus into the cytoplasm during cell division.
    reference_section_type: RESULTS
- id: PMID:16980972
  title: Structure of a human ASF1a-HIRA complex and insights into specificity of
    histone chaperone complex assembly.
  findings:
  - statement: >-
      CAF-1 p60 (CHAF1B) uses B-domain-like motifs to bind ASF1a, competing with
      HIRA for the same surface.
    supporting_text: >-
      CAF-1 p60 also uses B domain-like motifs for binding to ASF1a, thereby
      competing with HIRA.
    reference_section_type: ABSTRACT
- id: PMID:24981860
  title: Human-chromatin-related protein interactions identify a demethylase complex
    required for chromosome segregation.
  findings: []
- id: PMID:27705803
  title: A High-Density Map for Navigating the Human Polycomb Complexome.
  findings: []
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease
    networks.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
- id: PMID:7600578
  title: 'The p150 and p60 subunits of chromatin assembly factor I: a molecular link
    between newly synthesized histones and DNA replication.'
  findings:
  - statement: >-
      p150 and p60 directly interact and are both required for replication-dependent
      nucleosome assembly; they form complexes with newly synthesized H3 and
      acetylated H4.
    supporting_text: >-
      p150 and p60 directly interact and are both required for DNA
      replication-dependent assembly of nucleosomes.
    reference_section_type: ABSTRACT
    full_text_unavailable: true
- id: PMID:8858152
  title: Nucleosome assembly by a complex of CAF-1 and acetylated histones H3/H4.
  findings:
  - statement: >-
      The chromatin assembly complex contains the three CAF-1 subunits (p150, p60,
      p48) plus H3 and H4 and promotes DNA replication-dependent chromatin assembly.
    supporting_text: >-
      a chromatin assembly complex (CAC), which contains the three subunits of CAF-1
      (p150, p60, p48) and H3 and H4, and promotes DNA replication-dependent
      chromatin assembly.
    reference_section_type: ABSTRACT
    full_text_unavailable: true
- id: PMID:9614144
  title: Nucleosome assembly activity and intracellular localization of human CAF-1
    changes during the cell division cycle.
  findings:
  - statement: >-
      All three CAF-1 subunits (p150, p60, p48) are present through the cell cycle;
      p150/p60 are nuclear and concentrate at replication sites in S phase, and p60
      is hyperphosphorylated and inactive in mitosis.
    supporting_text: >-
      In interphase, p150 and p60 are bound to the nucleus, but they predominantly
      dissociate from chromatin during mitosis. During S phase, p150 and p60 are
      concentrated at sites of intranuclear DNA replication.
    reference_section_type: ABSTRACT
    full_text_unavailable: true
- id: file:human/CHAF1B/CHAF1B-uniprot.txt
  title: UniProt entry Q13112 (CAF1B_HUMAN)
  findings:
  - statement: >-
      CHAF1B is a component of the CAF-1 histone chaperone complex (RBBP4, CHAF1B,
      CHAF1A); CHAF1A binds directly to CHAF1B; interacts with histones H3.1, H3.2,
      H3.1t.
    supporting_text: >-
      Subunit of the CAF-1 complex that contains RBBP4, CHAF1B and CHAF1A. CHAF1A
      binds directly to CHAF1B.
    reference_section_type: OTHER
- id: file:human/CHAF1B/CHAF1B-deep-research-falcon.md
  title: Falcon deep research report for CHAF1B
  reference_review:
    relevance: HIGH
    correctness: UNVERIFIED
    review_notes: >-
      LLM-synthesized deep-research report (Edison/Falcon); claims are
      machine-aggregated and not independently verified, so marked UNVERIFIED.
      The report's own summary table usefully distinguishes CHAF1B/p60
      subunit-specific evidence from broader CAF-1 holo-complex inference. The
      strongest subunit-specific claims trace to the Liu et al. 2023 Science
      cryo-EM structure (add8673): that the p60 subunit is the principal H3-H4
      binding component, contacting histone H4 through its ventral beta-propeller
      surface and engaging a partially unfolded H3 region, and that CHAF1B is
      required for CAF-1 histone binding and nucleosome assembly activity. The
      report also surfaces a CHAF1B-specific genome-stability function (Shrestha
      et al. 2023, jcs.260944): CHAF1B depletion causes CENP-A mislocalization
      and chromosomal instability. Many other statements (PCNA recruitment,
      heterochromatin/H3K9me3-H3K27me3 maintenance, viral latency,
      transcriptional/cell-fate control, cancer overexpression) are attributed to
      the CAF-1 holo-complex or to CHAF1B knockdown phenotypes rather than to a
      direct, isolated p60 molecular activity, and should not be transferred to
      CHAF1B as subunit-specific molecular functions without primary-source
      verification. None of the underlying primary papers are in the publications
      cache; supporting_text quotes below are verbatim from this report, not from
      the primary articles.