Format

Send to

Choose Destination
Cell. 2018 May 31;173(6):1508-1519.e18. doi: 10.1016/j.cell.2018.04.015. Epub 2018 May 10.

The Cohesin Ring Uses Its Hinge to Organize DNA Using Non-topological as well as Topological Mechanisms.

Author information

1
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
2
Genome Centre, University of Sussex, Sussex House, Brighton BN1 9RH, UK.
3
Department of Molecular Biology and Biotechnology, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK.
4
DNA Metabolism Laboratory, IFOM, The FIRC Institute of Molecular Oncology, Via Adamello 16, 21139 Milan, Italy.
5
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. Electronic address: ashley.nasmyth@bioch.ox.ac.uk.

Abstract

As predicted by the notion that sister chromatid cohesion is mediated by entrapment of sister DNAs inside cohesin rings, there is perfect correlation between co-entrapment of circular minichromosomes and sister chromatid cohesion. In most cells where cohesin loads without conferring cohesion, it does so by entrapment of individual DNAs. However, cohesin with a hinge domain whose positively charged lumen is neutralized loads and moves along chromatin despite failing to entrap DNAs. Thus, cohesin engages chromatin in non-topological, as well as topological, manners. Since hinge mutations, but not Smc-kleisin fusions, abolish entrapment, DNAs may enter cohesin rings through hinge opening. Mutation of three highly conserved lysine residues inside the Smc1 moiety of Smc1/3 hinges abolishes all loading without affecting cohesin's recruitment to CEN loading sites or its ability to hydrolyze ATP. We suggest that loading and translocation are mediated by conformational changes in cohesin's hinge driven by cycles of ATP hydrolysis.

KEYWORDS:

SMC; chromosome condensation; cohesin; condensin; loop extrusion; sister chromatid cohesion

PMID:
29754816
PMCID:
PMC6371919
DOI:
10.1016/j.cell.2018.04.015
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center