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

doi:10.1016/j.molcel.2020.11.011

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

Molecular Biosciences

Research output: Contribution to journal › Article › peer-review

48 Scopus citations

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)
Pages (from-to)	1025-1038.e5
Journal	Molecular cell
Volume	80
Issue number	6
DOIs	https://doi.org/10.1016/j.molcel.2020.11.011
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

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10.1016/j.molcel.2020.11.011

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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.",

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AU - Sarker, Muzaddid

AU - Roy, Shamayita

AU - Malo, Catherine

AU - Pascal, John M.

AU - Marko, John F.

AU - D'Amours, Damien

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

Abstract

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Keywords

ASJC Scopus subject areas

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