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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Vydáno v:	Nature communications Ročník 8; číslo 1; s. 14011
Hlavní autoři:	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.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 30.01.2017 Nature Publishing Group Nature Portfolio
Témata:	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
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/ncomms14011