The Smc5/6 Core Complex Is a Structure-Specific DNA Binding and Compacting Machine

Diego Serrano, Gustavo Cordero, Ryo Kawamura, Aleksandr Sverzhinsky, Muzaddid Sarker, Shamayita Roy, Catherine Malo, John M. Pascal, John F. Marko, Damien D'Amours*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


The structural organization of chromosomes is a crucial feature that defines the functional state of genes and genomes. The extent of structural changes experienced by genomes of eukaryotic cells can be dramatic and spans several orders of magnitude. At the core of these changes lies a unique group of ATPases—the SMC proteins—that act as major effectors of chromosome behavior in cells. The Smc5/6 proteins play essential roles in the maintenance of genome stability, yet their mode of action is not fully understood. Here we show that the human Smc5/6 complex recognizes unusual DNA configurations and uses the energy of ATP hydrolysis to promote their compaction. Structural analyses reveal subunit interfaces responsible for the functionality of the Smc5/6 complex and how mutations in these regions may lead to chromosome breakage syndromes in humans. Collectively, our results suggest that the Smc5/6 complex promotes genome stability as a DNA micro-compaction machine.

Original languageEnglish (US)
Pages (from-to)1025-1038.e5
JournalMolecular cell
Issue number6
StatePublished - Dec 17 2020


  • DNA compaction
  • DNA repair
  • SMC
  • Smc5/6 complex
  • chromosome
  • genome stability
  • supercoiled DNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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