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.
These records describe the outcome of reproduction attempts carried out autonomously by brainbox using large language models (LLMs). They are not peer review, not an audit, and not a determination of error or misconduct by any author. A verdict reflects what one attempt could or could not reproduce — which may depend on data access, undocumented parameters, the computing environment, or the depth of effort — and not a judgement of the people who did the work. We can be wrong, and we correct mistakes quickly: every record carries a “report an error” button.
Assessment versions
Every reproduction run is kept as an immutable version — anchored to the data as it stood, with a tamper-evident chain hash. A rerun (e.g. after an author updates a deposit) adds a new version; the previous one stays on record.
-
v1 current initial assessment Score 80assessed: 2026-06-16 ⛓ cbb844ccadfb
✎ I am an author of this paper
Updated or fixed a deposit, or is there an erratum? Ask us to re-run the metrics. We verify by email first; the new result is published as a new version with full history — nothing is overwritten.
Provenance — full disclosure
When this reproduction was carried out, which methodology version was used, and by whom — so the record can be audited and checked independently.
- Reproduced
- 2026-06-16
- Rubric version
- v1.0
- Assessed by
-
🤖 AI curator · claude (ai-curator room) · v1.0 · run #1 2026-06-16no human curator yet
- Last updated
- 2026-08-05
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: opusThe paper tests whether sister chromatid cohesion is mediated by co-entrapment of sister DNAs inside a single cohesin ring, and asks whether cohesin associates with chromatin exclusively through topological entrapment or also via non-topological mechanisms dependent on its Smc1/3 hinge domain.
- ★ Sister chromatid cohesion is mediated by co-entrapment of both sister DNAs inside a single hetero-trimeric cohesin ring, perfectly correlating CD formation with cohesion finding
- ★ Cohesin can engage chromatin non-topologically (loading and translocation) without entrapping DNA, as shown by the smc1DDsmc3AAA hinge-lumen mutant finding
- ★ Cohesin's Smc1/3 hinge domain is critical for both topological and non-topological DNA association, implying DNAs enter the ring via hinge opening mechanism
- ★ Mutation of three conserved lysines in the Smc1 hinge moiety (smc1DDD) abolishes loading without affecting Scc2 recruitment at CENs or ATPase activity finding
- ★ CMs (single entrapped DNAs) reflect loading while CDs (co-entrapped sister DNAs) reflect cohesion finding
- Loading/translocation are driven by conformational changes in the hinge coupled to cycles of ATP hydrolysis mechanism
- ★ A minichromosome IP/BMOE crosslinking assay detects topological entrapment of DNA inside covalently circularized cohesin rings (CMs and CDs) method
- Single cohesin rings (one Scc1 copy) hold sister DNAs together, but multiple rings collaborate to form/maintain CDs finding
| Assay | System | Perturbation | Readout | Platform |
|---|---|---|---|---|
| Minichromosome immunoprecipitation with in vivo BMOE crosslinking, SDS denaturation, agarose gel and Southern blotting | S. cerevisiae carrying 2.3 kb circular minichromosome; 6C and 5C cysteine cohesin strains | cysteine-pair engineering at ring interfaces; various cohesin/cell-cycle mutants | CM (single entrapped DNA) and CD (co-entrapped sister DNAs) band intensities as % of total | — |
| 2D agarose gel electrophoresis with proteinase K in second dimension | S. cerevisiae 6C strain (K23889) with minichromosome | none (verification of DNA topology) | identity of CM/CD species as monomeric supercoiled DNAs | — |
| Western blot (anti-HA on Smc3) | S. cerevisiae 6C wild-type cohesin | BMOE crosslinking | crosslinked cohesin species / ring circularization (~20–25%) | — |
| Minichromosome IP across cell-cycle arrests | S. cerevisiae (scc2-45, cdc4-1, eco1-1, pds5-101 ts mutants; Sic1 overexpression; non-cleavable Scc1) | temperature-sensitive loss-of-function, G1/G2-M arrests, non-degradable Sic1, non-cleavable Scc1 | CM and CD formation | — |
| Minichromosome IP in polyploid tagging experiment | S. cerevisiae diploid and tetraploid strains (4x6C vs 1x6C/3x5C) | dilution of circularizable cohesin copies | ratio of CD to CM bands | — |
| Calibrated chromatin immunoprecipitation sequencing (ChIP-seq) | S. cerevisiae WT (K15426, Smc3-HA) and DDAAA mutant (K15424, smc3AAA-HA) | smc1DDsmc3AAA hinge-lumen neutralization | genome-wide cohesin occupancy along chromosomes II and VIII | — |
| ATPase activity assay | Purified WT (Smc1/Smc3/Scc1/Scc3) and mutant (smc1DD smc3AAA Scc1 Scc3) tetramers | smc1DDsmc3AAA mutation; ± DNA; + Scc2 | rate of ATP hydrolysis | — |
| Minichromosome IP with ATPase-site cohesin mutants | S. cerevisiae 6C strains with ectopic 2C Smc3-PK6 (WT, E1155Q, K38I) | Smc3 E1155Q (binds not hydrolyzes ATP), Smc3 K38I (cannot bind ATP) | CM and CD co-precipitation of minichromosome DNA | — |
- – Two DNA species (CMs and CDs) form uniquely in 6C cells; both are monomeric supercoiled DNAs (CM = single DNA, CD = sister pair) trapped within tripartite rings
- ▼ scc2-45, Smc3E1155Q and Smc3K38I cohesin fail to form CMs and CDs, showing dependence on Scc2 and ATP hydrolysis (despite E1155Q binding CENs efficiently)
- – DNA replication is required for CDs but not for CMs; Sic1 overexpression, cdc4-1, and non-cleavable Scc1 yield CMs without CDs
- – eco1-1 and pds5-101 mutants form CMs but not CDs; wpl1Δ restores CD formation in eco1 cells, confirming CD correlates with cohesion
- ▼ Shifting G2/M-arrested pds5-101 cells to restrictive temperature reduces CDs but not CMs 70% reduction in CDs
- – CD/CM ratio is unchanged when circularizable cohesin is diluted in tetraploids, showing single rings hold sister DNAs together ratio = 1.01, SD = 0.100
- ▼ smc1DDsmc3AAA (hinge-lumen neutralized) cohesin largely fails to form CMs and CDs yet associates stably with chromatin and loads genome-wide like WT CM ~20% and CD ~3% of WT levels
- – smc1DDsmc3AAA mutation has no effect on Scc2-stimulated ATPase activity (± DNA)
- fold_change CM band reduced to ~20% of WT in DDAAA mutant (smc1DDsmc3AAA minichromosome IP, 3 biological replicates)
- fold_change CD band reduced to ~3% of WT in DDAAA mutant (smc1DDsmc3AAA minichromosome IP, 3 biological replicates)
- other CD/CM ratio (4x6C)/(1x6C,3x5C) = 1.01, SD = 0.100 (tetraploid dilution experiment, 3 biological replicates)
- fold_change CDs reduced by 70% (pds5-101 G2/M shift to restrictive temperature, 3 biological replicates)
- count BMOE circularizes 20%–25% of 6C cohesin rings (in vivo crosslinking efficiency of wild-type 6C cohesin)
- other 2.3 kb circular minichromosome (reporter substrate used in entrapment 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.
-
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.
-
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.
-
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.
-
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.
-
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.
-
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)
-
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)
-
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)
-
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)
-
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)
-
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)
Citation network
Where this publication sits in the reproducibility-weighted citation graph — what it is built on, and what is built on it. Citation data from OpenAlex.
Assessed papers, coloured by verdict. Click a node to open it.
- No assessed neighbours yet — the network grows as more papers are assessed.
Data lineage
The datasets this paper uses (text-mined from the full text via Europe PMC), and which other assessed papers stand on the same data. A shared dataset is a factual link — not a judgement.
What was reproduced
The exact results taken into scope, with each reported value next to the value our attempt produced.
Assessments & scoring basis
Each contributor’s verdict, the per-question basis, and the auditable, itemised worksheet behind it.
An automated assessment. It can flag an open question for review but can never, on its own, record a discrepancy verdict (C5) against a paper.
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.
Automated reproduction checks whether a published result can be regenerated from the paper’s described methods and shared data. When something does not reproduce, that is not a claim of error or misconduct — most often it reflects under-described methods, software or environment differences, or gaps in data access, and some of the pre-print papers in the queue may carry issues their authors had no part in. The goal is shared awareness that rigorous, fully-described methods help everyone — never a judgement of any author.
Are you an author? We would genuinely like to hear from you — to clarify the record, add data or code, re-run the pipeline after an accession update, and publish your response right next to the assessment. Everything here is open and auditable.
🚩 Report an error in this record
Spotted something wrong — a verdict you’d contest, a data or value error, or a private detail that slipped through? Tell us, with a short justification. Authors and readers are equally welcome to write in; we review every report.
Prefer email, or the form below not working? Contact us at support@doesitreproduce.com.
Reproduction footprint
claude-opus-4-8Measured resources invested to assess this paper — sanitised (machine class only, no job ids/paths). Compute = HPC accounting (SLURM); tokens = the AI agent's session.