A Role for Chromatin Remodeling in Cohesin Loading onto Chromosomes.

Sofía Muñoz,Harshil Patel,Frank Uhlmann,Masashi Minamino,Corella S Casas-Delucchi

doi:10.1016/j.molcel.2019.02.027

Abstract

SummaryCohesin is a conserved, ring-shaped protein complex that topologically embraces DNA. Its central role in genome organization includes functions in sister chromatid cohesion, DNA repair, and transcriptional regulation. Cohesin loading onto chromosomes requires the Scc2-Scc4 cohesin loader, whose presence on chromatin in budding yeast depends on the RSC chromatin remodeling complex. Here we reveal a dual role of RSC in cohesin loading. RSC acts as a chromatin receptor that recruits Scc2-Scc4 by a direct protein interaction independent of chromatin remodeling. In addition, chromatin remodeling is required to generate a nucleosome-free region that is the substrate for cohesin loading. An engineered cohesin loading module can be created by fusing the Scc2 C terminus to RSC or to other chromatin remodelers, but not to unrelated DNA binding proteins. These observations demonstrate the importance of nucleosome-free DNA for cohesin loading and provide insight into how cohesin accesses DNA during its varied chromosomal activities.

Highlights

Following DNA replication, sister chromatids are held together in a process known as sister chromatin cohesion
The cohesin complex consists of two structural maintenance of chromosomes (SMC) proteins, Smc1 and Smc3, characterized by long flexible coiled coils that dimerize at a hinge domain
The remodels the structure of chromatin’ (RSC) ATPase Is Required for Cohesin Loading RSC chromatin remodeler inactivation leads to loss of cohesin from chromosomes and defective sister chromatid cohesion as well as reduced Scc2-Scc4 levels at cohesin loading sites (Baetz et al, 2004; Huang et al, 2004; Lopez-Serra et al, 2014)

Summary

Introduction

Following DNA replication, sister chromatids are held together in a process known as sister chromatin cohesion. This is essential for faithful chromosome segregation during cell divisions. The cohesin complex consists of two structural maintenance of chromosomes (SMC) proteins, Smc and Smc, characterized by long flexible coiled coils that dimerize at a hinge domain. At their far end lie globular ATPase heads that engage in the presence of ATP and are bridged by a kleisin subunit, Scc, to complete the ring. Apart from its prominent role in sister chromatid cohesion, cohesin takes part in many other chromosomal processes, including DNA repair and organization of the genome into chromatin loops (Dorsett and Strom, 2012; van Ruiten and Rowland, 2018)

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