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

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 (heterodim...

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Bibliographic Details
Published in:Nature communications Vol. 8; no. 1; p. 14011
Main Authors: Alt, Aaron, Dang, Hung Q., Wells, Owen S., Polo, Luis M., Smith, Matt A., McGregor, Grant A., Welte, Thomas, Lehmann, Alan R., Pearl, Laurence H., Murray, Johanne M., Oliver, Antony W.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 30.01.2017
Nature Publishing Group
Nature Portfolio
Subjects:
631/337/103
631/337/641/2002
631/45/535
631/45/612/1229
Adenosine Triphosphatases - chemistry
Binding Sites
Cell Cycle Proteins - chemistry
Cell Cycle Proteins - genetics
Cell Cycle Proteins - metabolism
Cell Line, Tumor
Cell Survival - physiology
Chromosomal Proteins, Non-Histone - chemistry
Chromosomal Proteins, Non-Histone - genetics
Chromosomal Proteins, Non-Histone - metabolism
Chromosomes
Cohesins
Crystallography, X-Ray
Deoxyribonucleic acid
DNA
DNA Damage
DNA Repair - physiology
DNA, Single-Stranded - metabolism
DNA-Binding Proteins - chemistry
Genomes
Humanities and Social Sciences
Humans
Life sciences
Models, Molecular
multidisciplinary
Multiprotein Complexes - chemistry
Mutagenesis, Site-Directed
Mutation
Phenotype
Protein Binding
Protein Domains - physiology
Protein Multimerization - physiology
Proteins
Recombinant Proteins - chemistry
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
Schizosaccharomyces - physiology
Schizosaccharomyces pombe Proteins - chemistry
Schizosaccharomyces pombe Proteins - genetics
Schizosaccharomyces pombe Proteins - metabolism
Science
Science (multidisciplinary)
Yeast
Yeasts
United Kingdom > UK
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary: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. Structural Maintenance of Chromosomes (SMC) complexes maintain genome integrity by regulating the segregation of chromosomes. Here, Alt et al . describe the structure of the heterodimeric Smc5/6-hinge from fission yeast and define functional features critical for Smc5/6’s cellular function.
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ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms14011