Reference - PMID:33176147 - DNA Binding by the Mis4 Scc2 Loader Promotes Topological DNA Entrapment by the Cohesin Ring.

Reference summary

PubMed ID

PMID:33176147

Title

DNA Binding by the Mis4 Scc2 Loader Promotes Topological DNA Entrapment by the Cohesin Ring.

Authors

Kurokawa Y, Murayama Y

Citation

Cell Rep 2020 Nov 10;33(6):108357

Publication year

2020

Abstract

Cohesin, a critical mediator of genome organization including sister chromatid cohesion, is a ring-shaped multi-subunit ATPase that topologically embraces DNA. Its loading and function on chromosomes require the Scc2-Scc4 loader. Using biochemical reconstitution, we show here that the ability of the loader to bind DNA plays a critical role in promoting cohesin loading. Two distinct sites within the Mis4 Scc2 subunit are found to cooperatively bind DNA. Mis4 Scc2 initially forms a tertiary complex with cohesin on DNA and promotes subsequent topological DNA entrapment by cohesin through its DNA binding activity, a process that requires an additional DNA binding surface provided by Psm3 Smc3 , the ATPase domain of cohesin. Furthermore, we show that mutations in the two DNA binding sites of Mis4 impair the chromosomal loading of cohesin. These observations demonstrate the physiological importance of DNA binding by the loader and provide mechanistic insights into the process of topological cohesin loading.

Annotation