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

• Published in: Nature communications 2017-01, Vol.8 (1), p.14011-14, Article 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: Article
• Language: English
• 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; 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
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms14011

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.