title: Specialized interfaces of Smc5/6 control hinge stability and DNA association.
abstract: 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.
authors.affiliation: Cancer Research UK DNA Repair Enzymes Group, Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, BN1 9RQ, UK.
authors.forename: Aaron
authors.initials: A
authors.lastname: Alt
authors.affiliation: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9RQ, UK.
authors.forename: Hung Q
authors.initials: HQ
authors.lastname: Dang
authors.affiliation: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9RQ, UK.
authors.forename: Owen S
authors.initials: OS
authors.lastname: Wells
authors.affiliation: Cancer Research UK DNA Repair Enzymes Group, Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, BN1 9RQ, UK.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Polo
authors.affiliation: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9RQ, UK.
authors.forename: Matt A
authors.initials: MA
authors.lastname: Smith
authors.affiliation: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9RQ, UK.
authors.forename: Grant A
authors.initials: GA
authors.lastname: McGregor
authors.affiliation: Dynamic Biosensors GmbH, Lochhamer Strasse, D-81252 Martinsreid/Planegg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Welte
authors.affiliation: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9RQ, UK.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Lehmann
authors.affiliation: Cancer Research UK DNA Repair Enzymes Group, Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, BN1 9RQ, UK.
authors.forename: Laurence H
authors.identifier: 0000-0002-6910-1809
authors.initials: LH
authors.lastname: Pearl
authors.affiliation: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9RQ, UK.
authors.forename: Johanne M
authors.initials: JM
authors.lastname: Murray
authors.affiliation: Cancer Research UK DNA Repair Enzymes Group, Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, BN1 9RQ, UK.
authors.forename: Antony W
authors.identifier: 0000-0002-2912-8273
authors.initials: AW
authors.lastname: Oliver
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology*; D004277:DNA, Single-Stranded / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010641:Phenotype; D011485:Protein Binding; D000072417:Protein Domains / Q000502:physiology; D055503:Protein Multimerization / Q000502:physiology; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000502:physiology; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000097722:Cohesins
chemical_list: D000251:Adenosine Triphosphatases; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; D011994:Recombinant Proteins; D029702:Schizosaccharomyces pombe Proteins; D000097722:Cohesins; C432931:SMC5 protein, human; C432932:SMC6 protein, human; C486628:Smc5 protein, S pombe; C108312:condensin complexes; C486630:smc6 protein, S pombe