RFWD3 (FANCW) — AIGR vs Affinage

RFWD3 (FANCW) — AIGR vs Affinage

Affinage record: run 2026-06-10 · 17 discoveries · self-eval win (faith 100%) · gates passed.

Agreement (brief)

Affinage and the AIGR review converge on the core biology, and the AIGR review was
already comprehensive here:

All 8 of Affinage's shared PMIDs (20173098, 21504906, 21558276, 26474068, 28575657,
28575658, 28691929, 33321094) were already cited and adjudicated in the AIGR review.

Disagreements

Topic Affinage says AIGR review says Verdict (who is right + why)
GO grounding of MF mechanism_profile gives only coarse parents: GO:0016874 ligase activity, GO:0140096 catalytic activity acting on a protein Specific GO:0061630 ubiquitin protein ligase activity AIGR right. Affinage's own note flags the profile as coarse; GO:0016874 (generic ligase, C–O/C–N/C–S bond formation) is arguably a different branch from thioester-forming Ub transfer. Do not import.
Localization grounding GO:0005634 nucleus + GO:0000228 nuclear chromosome nucleus + GO:0090734 site of DNA damage / GO:0035861 etc. AIGR right/finer. GO:0000228 (nuclear chromosome, the condensed structure) is not where an RPA/ssDNA-recruited fork factor is best placed; AIGR's damage-site/fork terms are more accurate.
Pathway layer Reactome DNA Repair, DNA Replication, Disease, Metabolism of proteins process terms grounded per-annotation AIGR right. "Metabolism of proteins" is a frequency-biased over-general parent (any ubiquitination event); uninformative for this gene.
p53 / MDM2 axis folded into the mechanistic narrative at similar prominence KEEP_AS_NON_CORE (single-group, secondary) AIGR right. Correct scoping; the axis is real (PMID:20173098) but peripheral to the replication-stress core.
TREX1 / STING immune role (PMID:41117130) listed as a 2025 finding absent AIGR defensibly conservative. Single 2025 paper, distinct pathway; not yet warranting a curated annotation. Noted, not imported.
ORC/ORCA stabilization (PMID:33044890) listed (self-rated Low confidence) absent AIGR right to omit. Affinage itself rates it Low; p53-context-dependent, single group.
Drosophila Mus302 (PMID:31900333) listed absent Correctly excluded — ortholog/evolution context, not human RFWD3 function; HR role is mammal-specific per that paper.

No factual conflicts requiring an AIGR reversal; the disagreements are the expected
coarse/over-general GO layer plus a few recent single-group over-reaches AIGR rightly excludes.

Papers incorporated into the review

PMID Supports How used
30530694 RFWD3 at unperturbed forks; PCNA/PIP binding stabilizes RFWD3; normal fork progression / DNA replication Added to references (relevance MEDIUM, VERIFIED) + verbatim supported_by on the GO:0031297 replication fork processing annotation
37036693 RFWD3 recruits ZRANB3 and stimulates fork remodeling/reversal (ZRANB3-epistatic) via PCNA ubiquitination Added to references (relevance MEDIUM, VERIFIED) + verbatim supported_by on the same GO:0031297 annotation

Both are full-text, RFWD3-focused functional studies that were missing from the review and
that corroborate/extend the (already accepted) replication-fork-processing role. No existing
decisions were weakened. Other Affinage-only PMIDs (32391871, 35905994, 40940676, 41117130,
41372167, 33044890, 31900333) were reviewed and not incorporated: they are corroborating
context, single-group recent findings, or non-human, none altering a curation call.

Net assessment

The AIGR review is stronger than the Affinage record on GO grounding, scoping, and evidence
adjudication — Affinage's mechanism_profile collapses to over-general (sometimes wrong-branch)
parents and should not be imported. Affinage's value here is its dense, dated PMID narrative,
which surfaced two legitimate RFWD3-focused mechanistic papers (PCNA/fork progression; ZRANB3/fork
remodeling) absent from the review. These were incorporated conservatively as corroborating
evidence on the existing fork-processing annotation. 0 new annotations, 2 papers incorporated,
review remains ✓ Valid.