Sanders, C. M., Sizov, D., Seavers, P. R. et al. (2 more authors) (2007) Transcription activator structure reveals redox control of a replication initiation reaction. Nucleic Acids Research, 35 (10). pp. 3504-3515. ISSN 0305-1048
Abstract
Redox changes are one of the factors that influence cell-cycle progression and that control the processes of cellular proliferation, differentiation, senescence and apoptosis. Proteins regulated through redox-sensitive cysteines have been characterized but specific ‘sulphydryl switches’ in replication proteins remain to be identified. In bovine papillomavirus type-1, DNA replication begins when the viral transcription factor E2 recruits the viral initiator protein E1 to the origin of DNA replication (ori). Here we show that a novel dimerization interface in the E2 transcription activation domain is stabilized by a disulphide bond. Oxidative cross-linking via Cys57 sequesters the interaction surface between E1 and E2, preventing pre-initiation and replication initiation complex formation. Our data demonstrate that as well as a mechanism for regulating DNA binding, redox reactions can control replication by modulating the tertiary structure of critical protein factors using a specific redox sensor.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2007 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | DNA-BINDING ACTIVITY; BOVINE PAPILLOMAVIRUS TYPE-1; E2 PROTEINS; TRANSACTIVATION DOMAIN; SUPEROXIDE DISMUTASE; CRYSTAL-STRUCTURE; CELL-CYCLE; IN-VITRO; E1; FIBROBLASTS |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 21 Nov 2016 13:44 |
Last Modified: | 21 Nov 2016 13:44 |
Published Version: | http://dx.doi.org/10.1093/nar/gkm166 |
Status: | Published |
Publisher: | Oxford University Press (OUP): Policy C - Option B |
Refereed: | Yes |
Identification Number: | 10.1093/nar/gkm166 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:107961 |