Cohesin Releases DNA through Asymmetric ATPase-Driven Ring Opening

Ahmed M.O Elbatsh,Judith H.I Haarhuis,Naomi Petela,Christophe Chapard,Alexander Fish,Patrick H Celie,Magda Stadnik,Dejan Ristic,Claire Wyman,René H Medema,Kim Nasmyth,Benjamin D Rowland

doi:10.1016/j.molcel.2016.01.025

Abstract

SummaryCohesin stably holds together the sister chromatids from S phase until mitosis. To do so, cohesin must be protected against its cellular antagonist Wapl. Eco1 acetylates cohesin’s Smc3 subunit, which locks together the sister DNAs. We used yeast genetics to dissect how Wapl drives cohesin from chromatin and identified mutants of cohesin that are impaired in ATPase activity but remarkably confer robust cohesion that bypasses the need for the cohesin protectors Eco1 in yeast and Sororin in human cells. We uncover a functional asymmetry within the heart of cohesin’s highly conserved ABC-like ATPase machinery and find that both ATPase sites contribute to DNA loading, whereas DNA release is controlled specifically by one site. We propose that Smc3 acetylation locks cohesin rings around the sister chromatids by counteracting an activity associated with one of cohesin’s two ATPase sites.

Highlights

Faithful chromosome segregation in mitosis is essential for genomic stability
Sororin is recruited to acetylated cohesin complexes and is essential for the protection against Wapl (Lafont et al, 2010; Nishiyama et al, 2010)
A Crucial Role for Smc1’s ATPase Domain in Cohesin’s Release from DNA From S phase until mitosis, cohesin rings are protected against Wapl

Summary

Introduction

Faithful chromosome segregation in mitosis is essential for genomic stability. This process is highly dependent on the cohesin complex, which holds together the sister chromatids of each chromosome. The cohesin complex consists of three core components (Smc, Smc, and Scc1) that together constitute a huge tripartite ring. Smc and Smc each have head domains, which together form a composite ABC-like ATPase, and have a second shared interface at the other end of their 50-nm-long coiled coils that is referred to as the hinge. Scc in turn bridges the head domains of both Smc proteins (Gruber et al, 2003; Haering et al, 2002). Cohesin is thought to hold together the sister chromatids by coentrapping them inside its ring-shaped structure (Haering et al, 2008)

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