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A new twist in the coil: functions of the coiled-coil domain of structural maintenance of chromosome (SMC) proteins

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Abstract

The higher-order organization of chromosomes ensures their stability and functionality. However, the molecular mechanism by which higher order structure is established is poorly understood. Dissecting the activity of the relevant proteins provides information essential for achieving a comprehensive understanding of chromosome structure. Proteins of the structural maintenance of chromosome (SMC) family of ATPases are the core of evolutionary conserved complexes. SMC complexes are involved in regulating genome dynamics and in maintaining genome stability. The structure of all SMC proteins resembles an elongated rod that contains a central coiled-coil domain, a common protein structural motif in which two α-helices twist together. In recent years, the imperative role of the coiled-coil domain to SMC protein activity and regulation has become evident. Here, we discuss recent advances in the function of the SMC coiled coils. We describe the structure of the coiled-coil domain of SMC proteins, modifications and interactions that are mediated by it. Furthermore, we assess the role of the coiled-coil domain in conformational switches of SMC proteins, and in determining the architecture of the SMC dimer. Finally, we review the interplay between mutations in the coiled-coil domain and human disorders. We suggest that distinctive properties of coiled coils of different SMC proteins contribute to their distinct functions. The discussion clarifies the mechanisms underlying the activity of SMC proteins, and advocates future studies to elucidate the function of the SMC coiled coil domain.

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Acknowledgements

We would like to thank members of the Onn lab for discussing the subject. This work was supported by grants from Israel Cancer Association 20170111 and Israel Science Foundation Grant 1099/16 to I.O.

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Correspondence to Itay Onn.

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Communicated by M. Kupiec.

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Matityahu, A., Onn, I. A new twist in the coil: functions of the coiled-coil domain of structural maintenance of chromosome (SMC) proteins. Curr Genet 64, 109–116 (2018). https://doi.org/10.1007/s00294-017-0735-2

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