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The multi-functional Smc5/6 complex in genome protection and disease

Nature Structural & Molecular Biology volume 30, pages 724–734 (2023)Cite this article

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Abstract

Structural maintenance of chromosomes (SMC) complexes are ubiquitous genome regulators with a wide range of functions. Among the three types of SMC complexes in eukaryotes, cohesin and condensin fold the genome into different domains and structures, while Smc5/6 plays direct roles in promoting chromosomal replication and repair and in restraining pathogenic viral extra-chromosomal DNA. The importance of Smc5/6 for growth, genotoxin resistance and host defense across species is highlighted by its involvement in disease prevention in plants and animals. Accelerated progress in recent years, including structural and single-molecule studies, has begun to provide greater insights into the mechanisms underlying Smc5/6 functions. Here we integrate a broad range of recent studies on Smc5/6 to identify emerging features of this unique SMC complex and to explain its diverse cellular functions and roles in disease pathogenesis. We also highlight many key areas requiring further investigation for achieving coherent views of Smc5/6-driven mechanisms.

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Fig. 1: Architecture of the Smc5/6 complex.
Fig. 2: Structures of different subunits and subcomplexes of the Smc5/6 complex.
Fig. 3: Multifaceted roles of Smc5/6 in recombinational repair and DNA replication.
Fig. 4: Summary of phenotypes caused by defective Smc5/6 in mammalian systems.

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Acknowledgements

We acknowledge NIGMS grant no. R35GM145260 (awarded to X.Z.). Due to space restrictions, references to early studies of Smc5/6 are not thoroughly included.

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  1. Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Xiao P. Peng

  2. Molecular Biology Program, Sloan Kettering Cancer Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Xiaolan Zhao

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Correspondence to Xiaolan Zhao.

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Peng, X.P., Zhao, X. The multi-functional Smc5/6 complex in genome protection and disease. Nat Struct Mol Biol 30, 724–734 (2023). https://doi.org/10.1038/s41594-023-01015-6

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