RFC3 (P38629, YNL290W) notes

2026-10-21 — Full re-review, independent of the ProtNLM2 predictions

Context: RFC3 is the closest experimentally characterised relative of the ProtNLM2 benchmark gene
SCHPO/rfc3 (O14003). This review was done without consulting any ProtNLM2 output.

Deep research

just deep-research-falcon yeast RFC3 --fallback perplexity-lite failed: falcon returned
"Failed to authenticate" and the perplexity-lite fallback returned HTTP 401 (insufficient quota).
No deep-research file was produced. The review is based on the cached publications (21 GOA-cited
papers plus PMID:14530260, PMID:15964801, PMID:15201901 fetched for this review) and the UniProt record.

Evolutionary grounding

• PANTHER: PTHR11669 (RFC / DNA pol III gamma-tau), subfamily PTHR11669:SF9, whose official name is
  "REPLICATION FACTOR C SUBUNIT 5". The pombe benchmark protein rfc3 (O14003) is in the same subfamily
  (family review interpro/panther/PTHR11669/PTHR11669-review.yaml), so S. cerevisiae RFC3 and
  S. pombe rfc3 are orthologs. PANTHER subfamily numbering does not follow yeast gene numbering.
• PAINT nodes: PTN000186209 (RFC small subunits: clamp loader activity, RFC complex, DNA repair),
  PTN000186208 (DNA-templated DNA replication; deeper node including bacterial donors),
  PTN000912313 (Rad17/Ctf18/Elg1 RFC-like complexes; yeast RFC3 SGD:S000005234 is a donor),
  PTN001705380 (nucleus). RFC3 is a donor for several of these; this is expected, not circular.
• DNA clamp unloader activity (GO:0061860): QuickGO shows yeast annotations only on the complex
  (CPX-422, IDA PMID:23499004); IBA rows sit on the large subunits (human RFC1, ATAD5). PomBase gives
  the S. pombe small subunits including rfc3 an IC annotation (PMID:16040599). PAINT did not propagate
  this to the small-subunit node; I treat that as deliberate and did not add a NEW row. It is raised as
  a suggested question.

Experimentally established in S. cerevisiae (with Rfc3 itself, or its complexes)

• Essential gene; purified Rfc3p alone has ssDNA-stimulated ATPase
  PMID:8302859
• Rfc3 supplies the arginine finger for the Rfc4 ATP site; strong PCNA contact
  PMID:14530260
• Subunit of RFC PMID:7651383, Rad24-RFC PMID:10660302,
  Ctf18-RFC PMID:11389843, Elg1-RFC [PMID:12912927; cryo-EM PMID:38427736].
• Rad24-RFC loads the 9-1-1 checkpoint clamp PMID:12604797.
• Ctf18-RFC unloads PCNA PMID:15964801.

Complex-level / inferred (not dissected for Rfc3)

• Sister chromatid cohesion: rfc4-ts and rfc5-1 alleles show precocious separation; no rfc3 allele
  tested in the cited papers. Kept as non-core.
• Mismatch repair / DNA repair: via general PCNA loading; review-level (TAS) and IBA. Kept as non-core.
• Leading strand elongation (IDA PMID:1346062) designation is "by analogy" with SV40; RFC acts on both
  strands. Kept as non-core; general strand elongation is core.

Decisions summary

• All 15 GO:0005515 protein binding IPI rows REMOVE (complex membership is captured by CC terms).
• Cytosol (hypoxia relocalization study) KEEP_AS_NON_CORE.
• All complex, clamp loader, ATPase, ATP binding, replication and nucleus rows ACCEPT.