Structural basis for topological regulation of Tn3 resolvase

Montaño, S. P., Rowland, S.-J., Fuller, J. R., Burke, M. E., MacDonald, A. I., Boocock, M. R., Stark, W. M. and Rice, P. A. (2023) Structural basis for topological regulation of Tn3 resolvase. Nucleic Acids Research, 51(3), pp. 1001-1018. (doi: 10.1093/nar/gkac733) (PMID:36100255) (PMCID:PMC9943657)

Abstract

Site-specific DNA recombinases play a variety of biological roles, often related to the dissemination of antibiotic resistance, and are also useful synthetic biology tools. The simplest site-specific recombination systems will recombine any two cognate sites regardless of context. Other systems have evolved elaborate mechanisms, often sensing DNA topology, to ensure that only one of multiple possible recombination products is produced. The closely related resolvases from the Tn3 and γδ transposons have historically served as paradigms for the regulation of recombinase activity by DNA topology. However, despite many proposals, models of the multi-subunit protein–DNA complex (termed the synaptosome) that enforces this regulation have been unsatisfying due to a lack of experimental constraints and incomplete concordance with experimental data. Here, we present new structural and biochemical data that lead to a new, detailed model of the Tn3 synaptosome, and discuss how it harnesses DNA topology to regulate the enzymatic activity of the recombinase.

• Item Type: Articles
• Additional Information: Funding: National Institutes of Health [R01 GM086826 to P.A.R., T32 GM007183 to J.R.F.]; Wellcome Trust [072552 to S.J.R., W.M.S.]; National Institutes of Health [P30 GM138395 to BioCAT beamline]. Funding for open access charge: University of Chicago.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: MacDonald, Dr Alasdair and Stark, Professor Marshall and Rowland, Dr Sally-Jane and Boocock, Dr Martin
• Authors: Montaño, S. P., Rowland, S.-J., Fuller, J. R., Burke, M. E., MacDonald, A. I., Boocock, M. R., Stark, W. M., and Rice, P. A.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: Nucleic Acids Research
• Publisher: Oxford University Press
• ISSN: 0305-1048
• ISSN (Online): 1362-4962
• Published Online: 14 September 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Nucleic Acids Research 51(3): 1001-1018
• Publisher Policy: Reproduced under a Creative Commons License