Publication Abstract from PubMed
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.
Transcription activator structure reveals redox control of a replication initiation reaction.,Sanders CM, Sizov D, Seavers PR, Ortiz-Lombardia M, Antson AA Nucleic Acids Res. 2007;35(10):3504-15. Epub 2007 May 3. PMID:17478495[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
