Interactions between proteins and nucleic acids are critical to many functions within the cell including replication, transcription, translation, and DNA repair. Proteins involved in these interactions may recognize either specific sequences, or structural irregularities within the nucleic acid derived from sequence dependent conformational preferences or from damage to the nucleic acid. These two types of recognition have been termed 'direct readout' and 'indirect readout'. The purpose of the recognition and binding may be to recruit other proteins to the site, or to perform modifications such as methylation or cleavage of the nucleic acid.
The Horton Lab is interested in the structural mechanisms of recognition and catalysis of nucleic acid binding proteins and enzymes, particularly those involved in DNA repair and epigenetics. Additionally, we are interested in the design of DNA binding proteins to serve in diagnosis and treatment of human disease.
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of the BMCB site and to an abstract of that particular paper.
Segal, D.J., J.W. Crotty, M. Bhakta, C.F. Barbas, III, and N.C. Horton. 2006. Structure of Aart, a designed six-finger zinc finger peptide, bound to DNA. Journal of Molecular Biology (in press).
Joshi, H.K., C. Etzkorn, L. Chatwell, J. Bitinaite, and N.C. Horton. 2006. Alteration of sequence specificity of the type II restriction endonuclease HincII through an indirect readout mechanism. Journal of Biological Chemistry 281: 23852-23869.
Little, E.J., and N.C. Horton. 2005. DNA-induced conformational changes in type II endonucleases; the structure of unliganded HincII. Journal of Molecular Biology 351: 76-88.
Crotty, J.W., C. Etzkorn, C.F. Barbas, III, D.J. Segal, and N.C. Horton. 2005. Crystallization and preliminary X-ray crystallographic analysis of Aart, a designed six-finger zinc-finger peptide, bound to DNA. Acta Crystallographica. Section F, Structural biology and Crystallization Communications 61: 573-576.
Etzkorn, C., and N.C. Horton. 2004. Mechanistic insights from the structures of HincII bound to cognate DNA cleaved from addition of Mg2+ and Mn2+. Journal of Molecular Biology 343: 833-849.
Etzkorn, C., and N.C. Horton. 2004. Ca2+ binding in the active site of HincII: implications for the catalytic mechanism. Biochemistry 43: 13256-13270.
