DNA recombination is necessary for the maintenance of genomic stability, as well as for the propagation of genetic diversity. Many recombination systems are also good model systems for addressing such basic questions as the strategies used by proteins to recognize and manipulate DNA, and to coordinate catalysis within multicomponent complexes. They also can be important biotechnology tools. This work focuses on understanding the structure and mechanism of two DNA recombinases that can address these topics in different and complementary ways: Flp and Rad51. Flp, a member of the """"""""tyrosine"""""""" or """"""""lambda integrase"""""""" family of DNA recombinases, catalyzes insertions, deletions, and inversions at specific DNA sequences. In addition to their importance in microbial survival, these enzymes, particularly Flp and Cre, are extensively used as tools for genetic manipulation. Rad51 and its prokaryotic homolog RecA are central players in the repair of double-strand breaks and other types of DNA damage, which, if not properly repaired, are carcinogenic. This project will combine crystallographic and biochemical experiments to study the structure and mechanism of these recombinases. The long-term goals are a better fundamental understanding of the strategies used by recombinases to rearrange genetic material, and of the strategies used to link enzymatic function to proper complex assembly. These studies will also help improve the usefulness of these recombinases as genetic tools.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM058827-09
Application #
7409587
Study Section
Molecular and Cellular Biophysics Study Section (BBCA)
Program Officer
Flicker, Paula F
Project Start
1999-02-01
Project End
2010-04-30
Budget Start
2008-05-01
Budget End
2010-04-30
Support Year
9
Fiscal Year
2008
Total Cost
$267,471
Indirect Cost
Name
University of Chicago
Department
Biochemistry
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
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