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研究领域

Our goal is to understand the fundamental mechanisms of transcriptional regulation at the level of macromolecular structure, function and interactions. Initiation of transcription, the primary point for control of gene expression, is regulated by the spontaneous assembly of regulatory protein and DNA containing complexes. Specific promoters are metabolically or developmentally regulated through coupling interactions between the site-specific protein-DNA interactions and protein-protein interactions, protein and DNA conformational transitions and allosteric transitions mediated by binding of regulatory ligands. Understanding the chemical basis for these macromolecular interactions provides the foundation to understand biological mechanisms of metabolic regulation, differentiation and development, and carcinogenesis.

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Multiple conformations of the cytidine repressor DNA-binding domain coalesce to one upon recognition of a specific DNA surface. Moody CL, Tretyachenko-Ladokhina V, Laue TM, Senear DF, Cocco MJ. Biochemistry. 2011 Aug 9;50(31):6622-32. Epub 2011 Jul 18. An unusual pattern of CytR and CRP binding energetics at Escherichia coli cddP suggests a unique blend of class I and class II mediated activation. Holt AK, Senear DF. Biochemistry. 2010 Jan 26;49(3):432-42 Molecular mechanisms of functional rescue mediated by P53 tumor suppressor mutations. Tan YH, Chen YM, Ye X, Lu Q, Tretyachenko-Ladokhina V, Yang W, Senear DF, Luo R. Biophys Chem. 2009 Nov;145(1):37-44. Epub 2009 Sep 1. Pressure dissociation of integration host factor-DNA complexes reveals flexibility-dependent structural variation at the protein-DNA interface. Senear DF, Tretyachenko-Ladokhina V, Opel ML, Aeling KA, Hatfield GW, Franklin LM, Darlington RC, Alexander Ross JB. Nucleic Acids Res. 2007;35(6):1761-72. Epub 2007 Feb 25. DNA deformation energy as an indirect recognition mechanism in protein-DNA interactions. Aeling KA, Steffen NR, Johnson M, Hatfield GW, Lathrop RH, Senear DF. IEEE/ACM Trans Comput Biol Bioinform. 2007 Jan-Mar;4(1):117-25. Indirect recognition in sequence-specific DNA binding by Escherichia coli integration host factor: the role of DNA deformation energy. Aeling KA, Opel ML, Steffen NR, Tretyachenko-Ladokhina V, Hatfield GW, Lathrop RH, Senear DF. J Biol Chem. 2006 Dec 22;281(51):39236-48. Epub 2006 Oct 11.

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