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Specialized interfaces of Smc5/6 control hinge stability and DNA association

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posted on 2023-06-09, 04:59 authored by Aaron Alt, Hung Q Dang, Owen Wells, Luis M Polo, Matthew Smith, Grant A McGregor, Thomas Welte, Alan LehmannAlan Lehmann, Laurence PearlLaurence Pearl, Jo Murray, Antony OliverAntony Oliver
The Structural Maintenance of Chromosomes (SMC) complexes: cohesin, condensin and Smc5/6 are involved in the organization of higher-order chromosome structure—which is essential for accurate chromosome duplication and segregation. Each complex is scaffolded by a specific SMC protein dimer (heterodimer in eukaryotes) held together via their hinge domains. Here we show that the Smc5/6-hinge, like those of cohesin and condensin, also forms a toroidal structure but with distinctive subunit interfaces absent from the other SMC complexes; an unusual ‘molecular latch’ and a functional ‘hub’. Defined mutations in these interfaces cause severe phenotypic effects with sensitivity to DNA-damaging agents in fission yeast and reduced viability in human cells. We show that the Smc5/6-hinge complex binds preferentially to ssDNA and that this interaction is affected by both ‘latch’ and ‘hub’ mutations, suggesting a key role for these unique features in controlling DNA association by the Smc5/6 complex.

History

Publication status

  • Published

File Version

  • Published version

Journal

Nature Communications

ISSN

2041-1723

Publisher

Nature Publishing Group

Volume

8

Page range

1-14

Article number

a14011

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2017-01-31

First Open Access (FOA) Date

2017-01-31

First Compliant Deposit (FCD) Date

2017-01-31

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