Format

Send to

Choose Destination
Mol Cell. 2016 Feb 18;61(4):575-588. doi: 10.1016/j.molcel.2016.01.025.

Cohesin Releases DNA through Asymmetric ATPase-Driven Ring Opening.

Author information

1
Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
2
Department of Biochemistry, University of Oxford, South Parks Road, OX1 3QU, Oxford, United Kingdom.
3
Division of Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
4
Department of Genetics, Cancer Genomics Netherlands, and Department of Radiation Oncology, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands.
5
Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. Electronic address: b.rowland@nki.nl.

Abstract

Cohesin 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.

PMID:
26895426
PMCID:
PMC4769319
DOI:
10.1016/j.molcel.2016.01.025
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

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