Team reveals structure of Smc5/6, a complex important to human health, first identified at Sussex over 25 years ago
By: Jessica Gowers
Last updated: Thursday, 25 August 2022
A study, led by a team of researchers based in the School of Life Sciences, has revealed the 3-dimensional structure of the budding yeast Smc5/6 complex using the technique of cryogenic electron microscopy (cryo-EM).
First identified by Sussex scientists nearly 27 years ago, the Smc5/6 complex has direct and emerging relevance to human health. Researchers at Sussex showed that alterations to the DNA encoding its component parts can lead to primordial dwarfism, insulin resistance, and the currently fatal condition known as LICS (Lung Disease, Immunodeficiency and Chromosome-breakage syndrome).
The complex also works as a so-called ‘restriction factor’, helping defend cells from invading viruses such as hepatitis B, herpes simplex and papillomavirus, a causative agent of both cervical and oropharyngeal cancers.
Whilst the study provides structural information for the yeast ‘version’ of the complex, there is sufficient similarity in terms of its cellular functions to directly inform studies examining its importance to human health.
Dr Jo Murray, Subject Chair for the Genome Damage and Stability Centre, said “The new structural information is an important step in understanding of how Smc5/6 protects cells against DNA damage. It has been made possible by the state-of-the-art microscopy and cryo-EM facilities in the new Wolfson Imaging Centre”.
Dr Antony Oliver, a Senior Research Fellow in the Genome Damage and Stability Centre was part of the team leading the research. Dr Oliver said, “It hoped that our study will aid scientists and clinicians working to treating individuals with LICS, as well as those developing new agents to protect against viral infection”.
Hallett et al., “Cryo-EM structure of the Smc5/6 holo-complex” is published in Nucleic Acids Research.