Authors
Costantino, L., Ye, T., Boardman, K., Xiang, S., Luo, J., Mu, Y., Ma, W., Koshland, D.
Abstract
Cohesin is a conserved protein complex that mediates sister chromatid cohesion, chromosome condensation, gene regulation, and DNA repair. These processes rely on cohesin's ability to tether sister chromatids and form chromatin loops, which depend on cohesin's ATPase activity and Eco1-mediated acetylation of two lysine residues (K112 and K113 in budding yeast) in its Smc3 subunit. How cohesin's ATPase activity and acetylation integrate to control cohesin functions remains poorly understood. Here, we analyzed chromatin architecture in yeast mutants with altered cohesin acetylation and/or ATPase activity. We find that acetylation of either K112 or K113 is sufficient to produce a wild-type chromosome structure with loops positioned at cohesin-associated regions (CARs), whereas loss of acetylation at both residues abolishes positioned loops, indicating that acetylation at either lysine alone can maintain wild-type chromatin architecture. We further show that a cohesin acetylation mutant, despite being defective in sister-chromatid tethering and thus failing to establish cohesion, still forms wild-type-like loops, while cohesion-competent mutants lack positioned loops. These results suggest that the activities required for cohesion and loop formation are mechanistically separable, arguing against passive loop capture. Moreover, a mutant with reduced ATPase activity showed a loop profile similar to wild type, indicating that cohesin with lower ATPase activity can still form wild-type chromatin architecture. By contrast, hyper-ATPase mutants accumulate positioned loops, suggesting that increasing ATPase activity can enhance loop processivity. Together, our findings support a multilayered regulatory model in which acetylation fine-tunes ATPase output and cohesin functions to shape genome architecture.
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bioRxiv
The authors list and abstract were imported from bioRxiv on 01 Nov 2025.
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