The Cohesin Ring Uses Its Hinge to Organize DNA Using Non-topological as well as Topological Mechanisms.
The main results reproduced: recomputed values matched the published ones within tolerance.
Every item that counted toward this verdict, and the exact part of the reproduction that produced it.
- ✓Same input data as the authors
- ✓Reported values were directly comparable
- ✓Reported values are derivable from the shared data
- ✓The central claim held under reproduction
- 🟡A deviation arose in the data or preprocessing
- 🟡A deviation was attributed to the published material
- 🟡The deviation was non-trivial in magnitude
- 🟡Overall, the reproduction showed a material discrepancy
A 0–100 reproducibility-quality score from the per-question grades, shown as a z-score: standard deviations above (+) or below (−) the mean of comparable assessments.
▸Reproduction agent’s raw note
DESCRIBED WELL ENOUGH -> FAITHFUL 1:1 ON THE FIGURE-GENERATING STEP. The repo (naomipetela/nasmythlab-ngs @ d7509c6) ships exactly the centromere-averaging scripts (chr_position.py + filter60.py) that produce the paper's averaged peri-centromeric cohesin profiles (Figs 3C/4/5/6B). I replayed filter60.py's exact +/-60kb CDEIII windows over the 34-sample GSE105005 deposited calibrated BigWig tracks (already OR-multiplied + 1e6-normalized per Methods) on «our HPC» («job», pyBigWig). The reproduced averaged meta-profiles match the published figures: a sharp CDEIII peak (all 17 IP tracks peak within ~0.25 kb of the anchor) decaying into peri-centromeric arms, with a flat untagged negative control. Comparative loading claims confirmed in direction: DDDAAA >= WT (2.18x, C2), Smc3-Scc1 fusion < WT (peak 0.91x / integrated 0.50x, C3), untagged ~ background (C4). NOT ATTEMPTED (the hard ~20%): re-deriving the occupancy ratio + dual-genome Bowtie2 alignment (sacCer3 + C. glabrata) from raw Ion Torrent reads -- underspecified read-counting and unnecessary since deposited tracks are pre-calibrated; and absolute y-axis scaling. No fabrication signs: every deposited track yields a coherent figure-consistent profile and the untagged control behaves correctly. All grades provisional; human reviewer compares reproduction/outputs/centromere_metaprofiles.png to Figs 3C/6B/4E.
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v1 current initial assessment Score 80assessed: 2026-06-16 ⛓ cbb844ccadfb
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- Reproduced
- 2026-06-16
- Rubric version
- v1.0
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🤖 AI curator · claude (ai-curator room) · v1.0 · run #1 2026-06-16no human curator yet
- Last updated
- 2026-09-19
Provisional, curator- or AI-assessed, and independently checkable. A reproduction outcome states what one attempt could reproduce — not a judgement of the authors.
Deep full-text extraction
Model: sonnetThe paper tests whether sister chromatid cohesion is mediated by topological co-entrapment of sister DNAs inside cohesin's tripartite ring, and whether cohesin's association with chromatin (loading, translocation) always requires such topological DNA entrapment.
- ★ Co-entrapment of sister DNAs inside cohesin rings (CDs) correlates perfectly with sister chromatid cohesion across multiple cell-cycle stages and mutants finding
- ★ Cohesin can load onto and translocate along chromatin in a non-topological manner, without entrapping DNA, as shown by the smc1DDsmc3AAA hinge mutant finding
- ★ DNA most likely enters cohesin rings through opening of the hinge interface rather than the Smc-kleisin interfaces, since hinge mutations but not Smc-kleisin fusions abolish entrapment mechanism
- ★ Three conserved lysines in the Smc1 hinge (smc1DDD) are required for cohesin loading/entrapment despite normal recruitment to CEN loading sites and normal ATPase activity finding
- ★ Loading and translocation are mediated by ATP-hydrolysis-driven conformational changes in cohesin's Smc1/3 hinge mechanism
- ★ Cohesive DNA-DNA linkages (CDs) are held together within individual (single) tripartite cohesin rings rather than by two interlinked rings (handcuff model) finding
- Wild-type cohesin can enable a cohesion/Pds5-binding-defective Scc1 mutant (V137K) to form CDs, implying functional collaboration between separate cohesin rings finding
- A BMOE crosslinking minichromosome immunoprecipitation assay can distinguish single-DNA entrapment (CMs) from sister-DNA co-entrapment (CDs) method
| Assay | System | Perturbation | Readout | Platform |
|---|---|---|---|---|
| Minichromosome IP with in vivo BMOE crosslinking / Southern blot | S. cerevisiae with 6C/5C cysteine-pair cohesin and 2.3 kb circular minichromosome | various mutants (scc2-45, smc3E1155Q, smc3K38I, eco1-1, wpl1Δ, pds5-101, smc1DDsmc3AAA, scc1V137K, cell-cycle arrests) | CM (single-DNA entrapment) and CD (sister-DNA co-entrapment) band intensity | agarose gel electrophoresis, Southern blotting |
| 2D gel electrophoresis with proteinase K digestion | S. cerevisiae 6C strain minichromosome IP | none | confirmation that CM/CD bands are monomeric supercoiled DNA species | 2D agarose gel electrophoresis |
| Calibrated ChIP-sequencing | S. cerevisiae, Smc3-HA tagged (WT and smc3AAA-HA) | smc1DDsmc3AAA hinge mutation, +/- endogenous untagged WT complex | genome-wide cohesin occupancy/ChIP profile along chromosomes II and VIII, CEN loading and spreading | calibrated ChIP-seq |
| ATPase activity assay | purified WT and smc1DDsmc3AAA tetramers (SMC1/SMC3/SCC1/SCC3) with Scc2 | smc1DDsmc3AAA hinge mutation, +/- DNA | rate of ATP hydrolysis | — |
| Western blot | S. cerevisiae 6C wild-type cohesin, HA-epitope on Smc3 | in vivo BMOE crosslinking | crosslinked cohesin ring species | Western blot |
| FACS analysis | S. cerevisiae strains (various mutants/arrests) | cell-cycle arrest/release (α factor, nocodazole, Sic1 non-degradable, cdc4-1) | DNA content / cell-cycle stage | flow cytometry (FACS) |
| Protein structural modeling | mouse Smc1/Smc3 hinge domain | neutralization of positively charged lumen residues (DDAAA mutations) | structural mapping of mutated residues | — |
- – CD/CM ratio unchanged between 4x6C and 1x6C,3x5C tetraploid strains, indicating single cohesin rings (not oligomers) hold CDs together ratio = 1.01, SD = 0.100
- ▼ smc1DDsmc3AAA mutant cohesin largely fails to form CMs and CDs despite loading stably onto chromatin CM ~20% and CD ~3% of WT levels
- – Calibrated ChIP-seq shows smc1DDsmc3AAA loads onto chromatin similarly or more than WT, and spreads from CEN sites like WT, despite failing to entrap DNA
- – smc1DDsmc3AAA has no effect on ATPase activity relative to WT
- ▼ eco1-1 mutants fail to form CDs at restrictive temperature but CM formation unaffected; wpl1Δ restores CD formation in eco1-1
- ▼ pds5-101 cells shifted to restrictive temperature after G2/M arrest lose CDs but not CMs CDs reduced ~70% (3 biological replicates)
- – scc1V137K mutant forms CDs only when wild-type Scc1 is co-expressed; with scc1-73 replacing WT, V137K forms CMs but not CDs
- – Non-degradable Sic1 or cdc4-1 arrest before S phase yields CM but not CD formation, showing CMs are not a byproduct of CDs
- ratio CD/CM(4x6C) / CD/CM(1x6C,3x5C) = 1.01, SD = 0.100 (tetraploid dilution experiment supporting single-ring (not oligomeric) CD formation)
- fold_change CM reduced to ~20% of WT (smc1DDsmc3AAA mutant minichromosome entrapment)
- fold_change CD reduced to ~3% of WT (smc1DDsmc3AAA mutant sister-DNA co-entrapment)
- fold_change CD reduction of 70% (pds5-101 cells shifted from permissive to restrictive temperature in G2/M)
- other 20%-25% of 6C cohesin rings circularized by BMOE (crosslinking efficiency of the minichromosome IP assay)
Statistical methods review
Model: opusA neutral, descriptive read of the statistical approach — what was done, and (for shared learning, not as criticism) what could also have been done.
The study is a molecular-genetics investigation that quantifies cohesin-DNA entrapment (CM and CD bands) across many yeast strains and cell-cycle states using an in vivo crosslinking/immunoprecipitation assay read out by Southern blotting, supplemented by calibrated ChIP-seq and in vitro ATPase assays. Results are reported descriptively as band intensities expressed as percentage of total lane signal, typically summarized as mean ± SD from three biological replicates, with conclusions drawn from observed differences and correlations rather than from formal hypothesis tests. No inferential statistical tests, p values, or multiplicity corrections are reported in the text provided.
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Differences between mutant and wild-type strains (e.g., reductions in CM/CD band intensity) were described qualitatively from replicate means without an accompanying inferential test.↳ Could also: A formal comparison such as an unpaired t-test or a non-parametric Mann-Whitney U test on the replicate-level quantifications could also have been reported. — Adding a test statistic and p value would attach an explicit measure of the evidence against chance variation to each comparison, complementing the descriptive means.
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Quantifications were summarized as mean ± SD from three biological replicates.↳ Could also: Reporting individual replicate data points (e.g., a scatter/dot plot overlaid on the mean) and/or a 95% confidence interval could also have been used. — With small n, showing every data point and a CI conveys the full spread and the precision of the estimate, which some readers find more informative than SD alone.
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Several conditions were compared against a common wild-type reference within the same experiments (e.g., multiple mutants vs. WT 6C).↳ Could also: A single one-way ANOVA with a post-hoc procedure (e.g., Dunnett's test for comparisons to a control) could also have been applied. — Analyzing the comparisons within one model would simultaneously account for the family of comparisons and control the family-wise error rate when many groups share a reference.
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Calibrated ChIP-seq profiles were presented as genome-wide occupancy traces shown for representative chromosomes, described by visual comparison of WT and mutant distributions.↳ Could also: Quantitative summaries across replicates (e.g., peak-level occupancy with a differential-binding framework such as DESeq2/edgeR or a correlation metric between profiles) could also have been reported. — A quantitative, replicate-aware summary would express the similarity or difference between WT and mutant occupancy as an estimated effect with associated uncertainty.
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The conclusion that the CD/CM ratio is unchanged between 4×6C and 6C/3×5C strains was supported by a ratio near 1 with a small SD.↳ Could also: An equivalence-testing approach (e.g., TOST) or a confidence interval around the ratio could also have been used to formalize 'no change.' — Equivalence testing frames a 'similarity' claim directly by bounding how large a difference can be ruled out, rather than relying on the absence of a detected difference.
Result convergence & founder nodes
Findings this paper shares with others that ran a comparable experiment. A node’s strength is how many independent papers report it (replication breadth) — not how often it is cited, so a heavily-replicated but under-cited founder still stands out.
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Cohesin tripartite rings topologically entrap single DNA molecules (CMs) and co-entrap sister chromatid pairs (CDs) as monomeric supercoiled species in vivoother saccharomyces-cerevisiae 2018×1papers★ This paper is the founder (earliest)
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A single cohesin ring co-entraps both sister DNAs (CD/CM ratio ~1.01 unchanged upon circularizable cohesin dilution in tetraploids), establishing that one ring is sufficient for topological sister chromatid cohesionother saccharomyces-cerevisiae none 2018×1papers★ This paper is the founder (earliest)
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ECO1 and PDS5 are required for sister chromatid co-entrapment (CD) but not single-DNA entrapment (CM); WPL1 deletion rescues CD formation in eco1 mutants, linking CD to cohesion establishmentother saccharomyces-cerevisiae down 2018×1papers★ This paper is the founder (earliest)
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Acute PDS5 inactivation reduces sister chromatid co-entrapment (CD) by ~70% without affecting single-DNA entrapment (CM), demonstrating PDS5 maintains cohesion after its establishmentother saccharomyces-cerevisiae down 2018×1papers★ This paper is the founder (earliest)
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SMC1-SMC3 hinge lumen charge neutralization (smc1DD smc3AAA) abolishes cohesin DNA ring entrapment (CM ~20%, CD ~3% of WT) despite normal genome-wide chromatin loading by ChIP-seq, demonstrating a hinge-specific non-topological loading stepother saccharomyces-cerevisiae down 2018×1papers★ This paper is the founder (earliest)
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SMC1-SMC3 hinge lumen charge neutralization (DDAAA) does not impair SCC2-stimulated ATPase activity in vitro, decoupling hinge-mediated DNA passage from ATPase functionother saccharomyces-cerevisiae none 2018×1papers★ This paper is the founder (earliest)
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Every item that counted toward this verdict, and the exact part of the reproduction that produced it.
This is a faithful 1:1 replay of the authors' own filter60.py centromere-averaging scripts over the deposited, pre-calibrated GSE105005 BigWig tracks, so the figure-generating computation and the central conclusion (cohesin peaks at CDEIII and decays into peri-centromeric arms; untagged is background) reproduce cleanly with no fabrication signs. The deviations sit on our side and are explainable: C3's integrated ratio (0.50) exceeds the paper's qualitative 'slightly less' because of a self-chosen window metric (peak ratio 0.91 matches), and C2 shows replicate spread (2.18 vs 0.82). The hard ~20% (calibration OR + raw dual-genome alignment, C5) was out of scope but the data is fully available. Overall: solid, qualitatively confirmed reproduction with minor metric-definition deviations — yellow, not critical.
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