354: How Cohesin Acetylation and ATPase Shape Chromatin Loops and Cohesion

Costantino L et al., PNAS - Costantino et al. dissect how Eco1-mediated acetylation of Smc3 (K112, K113) and cohesin ATPase activity separately regulate chromatin loop size, loop positioning, and sister chromatid tethering in budding yeast using Micro-C XL, ChIP, and biochemical ATPase assays. Key terms: cohesin, acetylation, ATPase, chromatin loops, sister chromatid cohesion.

Study Highlights:
Using a panel of budding yeast mutants, the authors show that acetylation of either Smc3 K112 or K113 is sufficient to produce positioned chromatin loops, while loss of both (Eco1 depletion) leads to expanded, unpositioned loops despite normal cohesin binding. K113 acetylation is required for sister chromatid cohesion (tethering), but cohesion-defective K113R mutants still form positioned loops, indicating looping can occur without tethering. K112 acetyl-mimic reduces loader-stimulated ATPase yet retains wild-type loop architecture, whereas hyper-ATPase mutants convert random loops into more positioned loops. The DE (low-ATPase) mutant produces long, unpositioned loops despite normal cohesin binding and Pds5 recruitment, indicating separable mechanisms downstream of acetylation and Pds5.

Conclusion:
Acetylation and ATPase activity separately tune cohesin's functions: acetylation at Smc3 K112/K113 helps position loops and control ATPase responsiveness, K113 acetylation is essential for tethering, and ATPase level biases cohesin toward random versus positioned loops, supporting active loop extrusion as the primary loop-forming mechanism.

Music:
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Article title:
Cohesin acetylation and ATPase activity control cohesion and loop architecture through distinct mechanisms

First author:
Costantino L

Journal:
PNAS

DOI:
10.1073/pnas.2531218123

Reference:
Costantino L, Ye T, Boardman K, Xiang S, Luo J, Mu Y, Ma W, Koshland D. Cohesin acetylation and ATPase activity control cohesion and loop architecture through distinct mechanisms. PNAS. 2026;123(17):e2531218123. doi:10.1073/pnas.2531218123.

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

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Episode link: https://basebybase.com/episodes/cohesin-acetylation-atpase-loop-architecture

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-04-30.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited the transcript sections describing cohesin functions (loop extrusion and tethering), Eco1-mediated Smc3 acetylation at K112/K113, ATPase regulation by Scc2/Scc4, mutations (K112R, K113R, K112Q, K113Q, DE, TI), Micro-C XL method and CARs, Pds5 involvement, and the active loop extrusion model versus loop capture.
- transcript topics: Cohesin functions: loop extrusion and sister chromatid tethering; Smc3 K112/K113 acetylation and Eco1; ATPase regulation by loader Scc2/Scc4 and acetylation; Mutant analyses: K112R, K113R, K112Q, K113Q, ECO1-AID, TI, DE; Micro-C XL methodology and CARs/positioned loops; Pds5 binding and loop regulation

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 6
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_titl...

Chapters

• (00:00:20) - Base by Base: The motor of cell division
• (00:05:37) - The chemical engine of cell cohesion
• (00:06:57) - Cohesin's passive loop capture model
• (00:10:22) - How does DNA cohesion work?
• (00:11:30) - Two Marked Tracks