Understanding protein-DNA interaction is essential in the fight of diseases at the genetic level. Restriction endonucleases are excellent model systems to study protein-DNA interaction because of their high specificity towards their recognition sequence. They are part of restriction-modification systems and serve as a primitive immune system in bacterial cells against bacteriophage infection by cutting the phage DNA with high specificity, while the host DNA is protected by a specific methylation within the recognition sequence. Additionally, the high specificity gives restriction endonucleases an important role in recombinant DNA technologies. I propose to study the structure-function of the FokI restriction endonuclease using a combination of biophysical methods. FokI belongs to a special subgroup of bipartite enzymes that cleave DNA nonspecifically at a defined distance outside of a non- palindromic recognition sequence. The bipartite nature of FoAl makes it an excellent candidate for the design of artificial enzymes. The studies will provide further understanding how recognition and catalysis are coupled (or de-coupled) in restriction endonucleases and will aid the design of restriction enzymes with new specificities.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM020015-03
Application #
6385056
Study Section
Molecular and Cellular Biophysics Study Section (BBCA)
Program Officer
Cassatt, James
Project Start
1999-05-31
Project End
Budget Start
2001-05-31
Budget End
2002-05-30
Support Year
3
Fiscal Year
2001
Total Cost
$45,560
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Physiology
Type
Schools of Medicine
DUNS #
114400633
City
New York
State
NY
Country
United States
Zip Code
10029