CHAF1B (Q13112) curation notes

Identity and overview

• CHAF1B = Chromatin assembly factor 1 subunit B (CAF-1 subunit B), also "CAF-I p60 subunit",
  "M-phase phosphoprotein 7" (MPHOSPH7/MPP7). UniProt Q13112; HGNC:1911; 559 aa.
  Synonyms in record: CAF1A, CAF1P60, MPHOSPH7, MPP7 [file:human/CHAF1B/CHAF1B-uniprot.txt].
• Maps to chromosome 21q22 (Down syndrome region) [file:human/CHAF1B/CHAF1B-uniprot.txt
  "Proteomes; UP000005640; Chromosome 21"; PMID:16780588 "human chromosome 21 proteins"].
• Domain architecture: N-terminal WD40 beta-propeller (7 WD repeats, ~res 1-385) plus a
  C-terminal disordered/low-complexity region (386-559) that is heavily phosphorylated
  [file:human/CHAF1B/CHAF1B-uniprot.txt; "Belongs to the WD repeat HIR1 family"].

Core function: medium subunit of CAF-1 histone H3-H4 chaperone

• CAF-1 (CHAF1A/p150, CHAF1B/p60, RBBP4/p48) is a three-subunit histone chaperone that
  assembles histone octamers onto replicating DNA in a cell-free system
  PMID:7600578.
• p60 contains WD repeats; p150 and p60 directly interact and are both required for
  DNA replication-dependent assembly of nucleosomes; deletion of the p60-binding domain
  from p150 prevents chromatin assembly PMID:7600578.
• p150 and p60 form complexes with newly synthesized histones H3 and acetylated H4
  PMID:7600578.
• The chromatin assembly complex (CAC) contains the three CAF-1 subunits (p150, p60, p48)
  plus H3 and H4 and promotes DNA replication-dependent chromatin assembly
  PMID:8858152.
• CAF-1 is the histone chaperone for the replication-coupled (DNA-synthesis-dependent)
  H3.1 deposition pathway; the H3.1 complex contains CAF-1 and is necessary for
  DNA-synthesis-dependent nucleosome assembly PMID:14718166.
• p60 binds histones H3.1/H3.2/H3.1t [file:human/CHAF1B/CHAF1B-uniprot.txt "Interacts with
  histones H3.1, H3.2 and H3.1t (PubMed:33857403)"].

Subcellular localization and cell cycle regulation

• All three CAF-1 subunits present throughout the cell cycle. In interphase p150 and p60 are
  nuclear; during S phase concentrated at sites of intranuclear DNA replication; they
  dissociate from chromatin during mitosis PMID:9614144.
• During mitosis the p60 subunit of inactive CAF-1 is hyperphosphorylated and displaced to
  the cytosol; progressively dephosphorylated from G1 to S/G2 [PMID:9614144 "In mitosis, the
  p60 subunit of inactive CAF-1 is hyperphosphorylated"; file:human/CHAF1B/CHAF1B-uniprot.txt
  PTM]. UniProt: Nucleus and Cytoplasm (M-phase cytoplasmic), DNA replication foci.
• Chromosome-21 protein localization screen independently observed CHAF1B nuclear at
  interphase, translocating to cytoplasm of daughter cells after cytokinesis
  PMID:16780588.
• HDA/HPA mass-spec/immunofluorescence localizations (cytosol, nucleoplasm) are high-throughput
  and consistent with the cell-cycle-dependent nucleo-cytoplasmic distribution; the cytosolic
  pool corresponds to the M-phase inactive form (colocalizes_with qualifier in GOA).

DNA repair link

• Phosphorylated CAF-1 (p60) is recruited to chromatin undergoing DNA repair after UV
  irradiation in G1, S or G2 [file:human/CHAF1B/CHAF1B-uniprot.txt PTM; FUNCTION
  ECO:0000269|PubMed:9813080 "assembles histone octamers onto DNA during replication and
  repair"]. Supports the DNA-repair-coupled chromatin assembly role (UniProtKB-KW DNA repair).

Protein-binding (IPI) annotations — assessment

The bare GO:0005515 protein binding IPI annotations capture interaction partners but are
uninformative as molecular function:
- PMID:16980972 — ASF1A (Q9Y294) and ASF1B (Q9NVP2): CAF-1 p60 uses B-domain-like motifs to
bind ASF1a, mutually exclusive with HIRA binding PMID:16980972. Functionally
meaningful (histone-chaperone hand-off) but term is generic protein binding.
- PMID:24981860 (ASF1A/Q9Y294), PMID:27705803, PMID:28514442, PMID:33961781, PMID:40205054 —
high-throughput AP-MS / interactome maps (BioPlex 2.0/3.0, Polycomb complexome, chromatin
interactome, multimodal cell maps). Generic, not specific MF. ASF1B (Q9NVP2) is the
recurrent interactor consistent with the ASF1-CAF-1 histone hand-off.

Recommended curation summary

• Core: histone chaperone (CAF-1 medium/p60 subunit), part of CAF-1 complex, DNA
  replication-dependent (and repair-coupled) chromatin/nucleosome assembly, nuclear.
• ACCEPT: CAF-1 complex (GO:0033186), DNA replication-dependent chromatin assembly
  (GO:0006335), chromatin (GO:0000785), nucleus (GO:0005634), histone binding (GO:0042393).
• MARK_AS_OVER_ANNOTATED: all bare protein binding (GO:0005515) IPI rows; broad
  protein-containing complex (GO:0032991).
• KEEP_AS_NON_CORE: cytoplasm/cytosol localizations (M-phase inactive pool), nucleoplasm.
• chromatin binding (GO:0003682, TAS) is acceptable but generic; histone binding is more
  informative MF.