Book of Abstracts: Albany 2009

category image Albany 2009
Conversation 16
June 16-20 2009
© Adenine Press (2008)

New Insights on Non-specific Protein-DNA Interactions: the DNase I Model

In the cell, DNA interacts almost continuously with proteins in order to ensure its biological functions. Specific and non-specific protein-DNA interactions imply the formation of intermolecular interfaces requiring electrostatic and structural complementarity of the related partners. Nevertheless, the mechanisms underlying the formation of non-specific protein-DNA complexes remain particularly obscure.

In this context, we chose to study the DNase I/DNA system as a representative and rather simple model of non-specific complex. DNase I is a glycoprotein which hydrolyzes the DNA phosphodiester linkages in presence of divalent cations, Ca2+ and Mg2+, and its activity depends on the DNA sequence.

Combining various experimental and theoretical techniques, we study DNA oligomers and DNase I, free and bound. We demonstrate that Ca2+ and Mg2+ are crucial for optimizing the electrostatic fit between DNA and enzyme. Preferential DNase I cleavages are found to be correlated to enhanced DNA dynamics that allow to minimize the cost of DNA deformation upon binding. Overall, this work highlights that the structure/function relationship in non-specific DNA-protein interaction parallels many features observed for specific DNA-protein recognition mechanisms.

Marc Guéroult1,2,*
Josephine Abi Ghanem1,2
Brahim Heddi2,a
Chantal Prévost2
Pierre Poulain1
Marc Baaden2
Brigitte Hartmann1,2

1UMR-S 665
Inserm/Univ. Paris Diderot-Paris 7 INTS
6 rue Alexandre Cabanel
75015 Paris
2CNRS/Univ. Paris Diderot-Paris 7
IBPC, 13 rue Pierre et Marie Curie
75005 Paris
apresent address:
School of Physical & Mathematical Sciences
Nanyang Technological University
21 Nanyang Link
SPMS PAP 05-08
Singapore 637371