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Biochemistry
R. Bentley
J. Brodsky
J. Franzen
P. Grabowski
J. Hempel
L. Jen-Jacobson
K. Kiselyov
C. Peebles
J. Rosenberg
A. Schwacha
Cell
Biology
J. Brodsky
A. Chung
J. Hildebrand
L. Jacobson
N. Kaufmann
K. Kiselyov
J. Pipas
M.-T. Sáens-Robles
W. Saunders
C. Walsh
Computational
Biology
M. Grabe
J. Lawrence
J. Rosenberg
Developmental
Biology
G. Campbell
D. Chapman
J. Hildebrand
B. Roman
S. Shostak
B. Stronach
V. Twombly
Ecology
T.-L. Ashman
W. Carson
W. Coffman
S. Kalisz
T. Katzner
R. Relyea
S. Tonsor
B. Traw
Evolution
T.-L. Ashman
A. Bledsoe
S. Kalisz
J. Lawrence
Z.-X. Luo
R. Relyea
S. Shostak
S. Tonsor
B. Traw
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
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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.
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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
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Phone, FAX, Internet
Office : (412) 624-4969
Lab : (412)-624-6450
FAX : (412) 624-4759
Email : ljen+@pitt.edu
Web :
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