The acetyltransferase Eco1 elicits cohesin dimerization during S phase

Abstract Sister chromatid cohesion is established by Eco1 in S phase. Nevertheless, the exact consequence of Eco1-catalyzed acetylation is unknown, and the cohesive state remains highly controversial. Here we show that self-interactions of cohesin subunits Scc1/Rad21 and Scc3 occur in a DNA replication-coupled manner in both yeast and human. Through cross-linking mass spectrometry and VivosX analysis of purified cohesin, we show that a subpopulation of cohesin may exist as dimers. Importantly, cohesin-cohesin interaction becomes significantly compromised when Eco1 is depleted. On the other hand, deleting either deacetylase Hos1 or Eco1 antagonist Wpl1/Rad61 results in an increase (e.g., from ∼20% to 40%) of cohesin dimers. These findings suggest that cohesin dimerization is controlled by common mechanisms as the cohesion cycle, thus providing an additional layer of regulation for cohesin to execute various functions such as sister chromatid cohesion, DNA repair, gene expression, chromatin looping and high-order organization.Author Summary Cohesin is a ring that tethers sister chromatids since their synthesis during S phase till their separation in anaphase. According to the single-ring model, one ring holds twin sisters. Here we show a conserved cohesin-cohesin interaction from yeast to human. A subpopulation of cohesin is dimerized concomitantly with DNA replication. Cohesin dimerization is dependent on the acetyltransferase Eco1 and counteracted by the anti-establishment factor Wpl1 and deacetylase Hos1. Approximately 20% of cellular cohesin complexes are measured to be dimers, close to the level of Smc3 acetylation by Eco1 in vivo. These findings provide evidence to support the double-ring model in sister chromatid cohesion..

Medienart:

Preprint

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

bioRxiv.org - (2020) vom: 10. Juli Zur Gesamtaufnahme - year:2020

Sprache:

Englisch

Beteiligte Personen:

Shi, Di [VerfasserIn]
Zhao, Shuaijun [VerfasserIn]
Zuo, Mei-Qing [VerfasserIn]
Zhang, Jingjing [VerfasserIn]
Hou, Wenya [VerfasserIn]
Dong, Meng-Qiu [VerfasserIn]
Cao, Qinhong [VerfasserIn]
Lou, Huiqiang [VerfasserIn]

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doi:

10.1101/2020.02.07.938530

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

XBI000726931