Dr. Linda Jen-Jacobson

Genetics
K. Arndt
T.-L. Ashman
G. Campbell
D. Chapman
G. Hatfull
J. Hildebrand
L. Jacobson
S. Kalisz
J. Martens
W. Saunders
B. Stronach
S. Tonsor
R. Wood

Microbiology
J. Boyle
G. Hatfull
R. Hendrix
J. Lawrence
J. Pipas
M. Popa
R.L. Duda
S. Godfrey
V. Oke

Molecular Biology
K. Arndt
J. Franzen
P. Grabowski
G. Hatfull
R. Hendrix
L. Jen-Jacobson
J. Martens
C. Peebles
J. Pipas
J. Rosenberg
A. Schwacha
C. Walsh

Plant Biology
T.-L. Ashman
W. Carson
S. Kalisz
V. Oke
C. Partanen
S. Tonsor
B. Traw

Science Education
A. Bledsoe
K. Curto
L. Daniels
S. Godfrey
N. Kaufmann
C. LaFave
J. Newman
E. Polinko
M. Popa
L. Roberts
T. Seiflein
R. Sherwin
A. Slinskey Legg

Structural Biology
M. Grabe
J. Hempel
R. Hendrix
L. Jen-Jacobson
J. Rosenberg
A. VanDemark

Former Faculty

Photo of Dr.
Jen-Jacobson

Molecular Mechanisms of Sequence-Specificity in Protein-DNA Interactions; Structure-Function Relationships, Energetics and Conformational Dynamics in Proteins and Nucleic Acids

Professor

Dr. Jen-Jacobson received her Ph.D. in 1967 from the University of Illinois and joined the Department in 1975.

Currently, Dr. Jen-Jacobson is accepting graduate students in her laboratory. Dr. Jen-Jacobson is accepting undergraduate researchers, and does sponsor students in other laboratories.

Professional Interests - Publications - Contact Information - Lab Personnel

Professional Interests of Linda Jen-Jacobson

The long-range objective of our research is to gain insight into the molecular determinants for high DNA site selectivity by proteins. Our strategy uses the conceptual and analytical methods of biophysics and structural biochemistry in combination with the manipulation methods of synthetic chemistry and of molecular genetics, and emphasizes the concerted use of a number of tools. We are currently combining high resolution "structural-perturbation" methods with isothermal titration calorimetry to obtain complete thermodynamic profiles (i.e., changes in enthalpy, entropy, heat capacity) for protein-DNA complex formation, together with computational modeling to complement our interpretations. Some of our current work focuses on the thermodynamic consequences of molecular strain, experimental measurement of solvation changes upon binding, and the molecular properties of mutant proteins with reduced specificity.

Our ongoing principal goal is to adduce general principles applicable to most or all sequence-specific DNA-binding proteins. Our work points to the importance of time-dependent (dynamic) characteristics of protein-DNA complexes, including binding- dependent conformational transitions in the proteins and DNA and configurational (conformational and vibrational) fluctuations in the protein-DNA complexes, so we are pursuing spectroscopic methods (Nuclear Magnetic Resonance and Electron Spin Resonance) that inform us about these dynamics. A profound understanding of these basic physicochemical principles and their applications is what we will ultimately need to develop methods for knowledge-based drug design and design of macromolecules to fulfill specific biological functions.

Publication Archive
37 Citations
30 Abstracts
20 PDFs

Recent Publications of Linda Jen-Jacobson

Mikheikin, A.L., H.K. Lin, P. Mehta, L. Jen-Jacobson, and M.A. Trakselis (2009) A trimeric DNA polymerase complex increases the native replication processivity. Nucleic Acids Res. 37:7194-7205

Dylla-Spears, R., J.E. Townsend, L.L. Sohn, L. Jen-Jacobson, and S.J. Muller (2009) Fluorescent Marker for Direct Detection of Specific dsDNA Sequences. Anal. Chem. 81:10049-10054 (PDF Reprint: 2.8 MB)

VanderVeen, L.A., T.M. Harris, L. Jen-Jacobson, and L.J. Marnett (2008) Formation of DNA-protein cross-links between gamma-hydroxypropanodeoxyguanosine and EcoRI. Chem. Res. Toxicol. 21:1733-1738 (PDF Reprint: 2.8 MB)

Stone, K.M., J.E. Townsend, J. Sarver, P.J. Sapienza, S. Saxena, and L. Jen-Jacobson (2008) Electron spin resonance shows common structural features for different classes of EcoRI-DNA complexes. Angew. Chem. Int. Ed. Engl. 47:10192-10194 (PDF Reprint: 784 kb)

Jen-Jacobson, L., and L.A. Jacobson (2008) The role of water and the effects of small ions in site-specific protein-DNA interactions. Pp in Structural Biology of Protein-Nucleic Acid Interactions, Rice, P.A., and C. Correll, Ed. Royal Society of Chemistry Publishing, Cambridge

Sapienza, P.J., J.M. Rosenberg, and L. Jen-Jacobson (2007) Structural and thermodynamic basis for enhanced DNA binding by a promiscuous mutant EcoRI endonuclease. Structure 15:1368-1382 (PDF Reprint: 2.6 MB)

Sapienza, P.J., C.A. Dela Torre, W.H. .4.t. McCoy, S.V. Jana, and L. Jen-Jacobson (2005) Thermodynamic and kinetic basis for the relaxed DNA sequence specificity of "promiscuous" mutant EcoRI endonucleases. J. Mol. Biol. 348:307-324 (PDF Reprint: 575 kb)

Kurpiewski, M.R., L.E. Engler, L.A. Wozniak, A. Kobylanska, M. Koziolkiewicz, W.J. Stec, and L. Jen-Jacobson (2004) Mechanisms of coupling between DNA recognition specificity and catalysis in EcoRI endonuclease. Structure 12:1775-1788 (PDF Reprint: 363 kb)

Shuttleworth, G., M.J. Fogg, M.P. Kurpiewski, L. Jen-Jacobson, and B.A. Connolly (2004) Recognition of the pro-mutagenic base uracil by family B DNApolymerases from Archaea. J. Mol. Biol. 337:621-634 (PDF Reprint: 2.0 MB)

Engler, L.E., P. Sapienza, L.F. Dorner, R. Kucera, I. Schildkraut, and L. Jen-Jacobson (2001) The energetics of the interaction of BamHI endonuclease with its recognition site GGATCC. J. Mol. Biol. 307:619-636 (PDF Reprint: 1.7 MB)

Connolly, B.A., H.H. Liu, D. Parry, L.E. Engler, M.R. Kurpiewski, and L. Jen-Jacobson (2001) Assay of restriction endonucleases using oligonucleotides. Methods Mol. Biol. 148:465-490

Watrob, H., W. Liu, Y. Chen, S.G. Bartlett, L. Jen-Jacobson, and M.D. Barkley (2001) Solution conformation of EcoRI restriction endonuclease changes upon binding of cognate DNA and Mg²⁺ cofactor. Biochemistry 23:683-692

Jen-Jacobson, L., L.E. Engler, J.T. Ames, M.R. Kurpiewski, and A. Grigorescu (2000) Thermodynamic parameters of specific and nonspecific protein-DNA binding. Supramol. Chem. 12:143-160 (PDF Reprint: 1.6 MB)

Jen-Jacobson, L., L. Engler, and L.A. Jacobson (2000) Structural and thermodynamic strategies for site-specific DNA binding proteins. Structure 8:1015-1023 (PDF Reprint: 242 kb)

How to Contact Linda Jen-Jacobson

US Mail
University of Pittsburgh
Department of Biological Sciences
320 Clapp Hall
4249 Fifth Avenue
Pittsburgh, PA 15260

Phone, FAX, Internet
Office : (412) 624-4969
Lab : (412)-624-6450
FAX : (412) 624-4759
Email : ljen+@pitt.edu
Web :

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