Abstract
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 language | English (US) |
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Pages (from-to) | 1025-1038.e5 |
Journal | Molecular cell |
Volume | 80 |
Issue number | 6 |
DOIs | |
State | Published - Dec 17 2020 |
Funding
We thank members of the D’Amours laboratory for their comments on the manuscript and Peter Stirling (UBC) for sharing nse1/3/4 mutant strains. This work was supported by grants from CIHR ( FDN-167265 to D.D.) and NSERC ( DG RGPIN-2015-05776 to J.M.P.). Work at NU was supported by NIH grants R01-GM105847 and U54-CA193419 (CR-PS-OC) and a subcontract to grant U54-DK107980 (4D Nucleome). D.D. is supported by a Canada Research Chair in Chromatin Dynamics & Genome Architecture . D.S. and A.S. were supported by post-doctoral fellowships from the FRQS ( 29086 and 33382 ) and NSERC ( 487769-2016 ), respectively.
Keywords
- DNA compaction
- DNA repair
- SMC
- Smc5/6 complex
- chromosome
- genome stability
- supercoiled DNA
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology