Nancy C. Horton
Associate Professor of Biochemistry and Molecular Biophysics
Ph.D. 1994, University of Pennsylvania
Protein-nucleic acid recognition, enzymology, X-ray crystallography, kinetics, protein dynamics, DNA repair
Research Interests
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.
Selected Publications
Early Interrogation and Recognition of DNA Sequence by Indirect Readout. Little, E.J., Babic, A.C. & Horton, N.C. Structure 16, 1828-1837 (2008).
DNA Distortion and Specificity in a Sequence Dependent Endonuclease. Babic, A.C., Little, E.J., Manohar, V.M., Bitinaite, J. & Horton, N.C. J. Mol. Biol. 383, 186-204 (2008). [pdf]
The Structure of SgrAI bound to DNA: Recognition of an 8 base pair target. Dunten, P.W., Little, E.J., Gregory, M.T., Manohar, V.M., Dalton, M., Hough, D., Bitinaite, J. & Horton, N.C. Nucleic Acids Research, 36, 5405-5016 (2008). [pdf]
DNA Nucleases. N.C. Horton. In Protein-Nucleic Acid Interactions: Structural Biology; Carl C. Correll, Ed.; RSC Publishing: Cambridge, United Kingdom, 2008. [pdf]
Structure of Aart, a designed six-finger zinc finger peptide, bound to DNA. Segal D.J., Crotty J.W., Bhakta M.S., Barbas C.F. 3rd, Horton N.C., J. Mol Biol. Oct 20; 363 (2): (2006) 405-21. [pdf]
Alteration of Sequence Specificity of the Type II restriction endonuclease HincII through an indirect readout mechanism. Joshi, H.K., Etzkorn, C., Chatwell, L., Bitinaite, J., N.C. Horton, J Biol Chem. 281, (2006) 23852-69. [pdf]
DNA induced conformational changes in type II endonucleases; the structure of unliganded HincII. Little, E.J. and N. C. Horton, J. Mol. Biol. 351, (2005) 76-88. [pdf]
Crystallization and preliminary X-ray crystallographic analysis of Aart, a designed six-finger zinc-finger peptide, bound to DNA. Crotty, J.W., Etzkorn, C., Barbas, III, C.F., Segal, D.J. and N. C. Horton, Acta. Cryst. F61, (2005) 573-576. [pdf]
Mechanistic insights from the structures of HincII bound to cognate DNA cleaved from addition of Mg2+ and Mn2+. Etzkorn, C., and N.C. Horton, Journal of Molecular Biology 343: (2004) 833-849. [pdf]
Ca2+ Binding in the active site of HincII: implications for the catalytic mechanism. Etzkorn, C., and N.C. Horton, Biochemistry 43: (2004) 13256-13270. [pdf]
DNA cleavage by EcoRV endonuclease: two metal ions in three metal ion binding sites. N.C. Horton & J.J. Perona, Biochemistry 43, (2004) 6841-6857. [pdf]
Electrostatic contributions to site specific DNA cleavage by EcoRV endonuclease. N.C. Horton, C. Otey, S. Lusetti, M.D. Sam, J. Kohn, A.M. Martin, V. Ananthnarayan, & J.J. Perona, Biochemistry, 41, (2002) 10754-10763. [pdf]
Sequence selectivity and degeneracy of a restriction endonuclease mediated by DNA intercalation. N.C. Horton, L.F. Dorner & J.J. Perona, Nature Structural Biology, 9, (2002) 42-47. [pdf]
Catalytic efficiency and sequence selectivity of a restriction endonuclease modulated by a distal manganese ion binding site. M.D. Sam, N.C. Horton, T.A. Nissan & J.J. Perona, Journal of Molecular Biology 306, (2002) 851-861. [pdf]
Making the most of metal ions. N.C. Horton & J.J. Perona, Nature Structural Biology, 4, (2001) 290-293. [pdf]
Mechanism of inhibition of phosphoryl transfer in EcoRV by 3'S phosphorothiolates. N.C. Horton, B.A. Connolly, & J.J. Perona, JACS 122, (2000) 3314-3324. [pdf]
Crystallographic snapshots along a protein-induced DNA bending pathway. N.C. Horton & J.J. Perona, Proc. Natl. Acad. Sci, USA 97, (2000) 5729-5734. [pdf]
Crystallization and preliminary diffraction analysis of the HincII restriction endonuclease -DNA complex. N.C. Horton, L.F. Dorner, I. Schildkraut & J.J. Perona, Acta Cryst. D. 55, (1999) 1-3. [pdf]
Divalent metal dependence of site-specific DNA binding in EcoRV endonuclease. A.M. Martin, N.C. Horton, S. Lusetti, N.O. Reich, & J.J. Perona, Biochemistry 38, (1999) 8430-8439. [pdf]
Role of protein-induced bending in the specificity of DNA recognition: Crystal structure of EcoRV endonuclease complexed with d(AAAGAT)+d(ATCTT). N.C. Horton & J.J. Perona, J. Mol. Biol. 277, (1998) 779-787. [pdf]
Recognition of flanking DNA sequences by EcoRV endonuclease involves alternative patterns of water-mediated contacts. N.C. Horton & J.J. Perona,
J. Biol. Chem. 273, (1998) 21721-21729. [pdf]
Metal ion mediated substrate-assisted catalysis in type II restriction endonucleases. N.C. Horton, K.J. Newberry & J.J. Perona, Proc. Natl. Acad. Sci., USA 95, (1998) 13489-13494. [pdf]
Cation binding to the integrin CD11b I domain and activation model assessment. E.T. Baldwin, R.W. Sarver, G.L. Bryant,Jr. , K.A. Curry, M.B. Fairbanks, B.C. Finzel, R.L. Garlick, R.L. Heinrikson, N.C. Horton, L.C. Kelley, A.M. Mildner, J.B. Moon, J.E. Mott, V.T. Mutchler, C.C. Tomich, K.D. Watenpaugh, & V.H. Wiley, Structure 6, (1998) 923-935. [pdf]
Escherichia coli lac repressor-lac operator interaction and the influence of allosteric effectors. N. Horton, M. Lewis, & P. Lu, J. Mol. Biol. 265, (1997) 1-7. [pdf]
The structure of an RNA/DNA hybrid: a substrate of the ribonuclease activity of HIV-1 reverse transcriptase. N.C. Horton, & B.C. Finzel, J. Mol. Biol. 264, (1996) 521-533. [pdf]
Crystal structure of the lactose operon repressor and its complexes with DNA and inducer. M. Lewis, G. Chang, N.C. Horton, M.A. Kercher, H.C. Pace, M.A. Schumacher, R.G. Brennan, & P. Lu, Science 271, (1996) 1201-1332. [pdf]
Calculation of the free energy of association for protein complexes. N. Horton, & M. Lewis, Protein Science 1, (1992) 169-181. [pdf]