We are examining DNA damage for two goals (1) relating specific lesions with biological activity; and, (2) gain better understanding of protein-DNA interactions. Specifically, we are focusing on mechanisms of chemical mutagenesis and the molecular biology of DNA repair. We have modeled the FPG zinc finger-DNA complex based on NMR and X-ray crystallographic structures. The FPG zinc-finger moiety was based on the NMR structure of XFIN. Using molecular dynamics and combinatorial library data for preferential patterns of helix side chains binding to DNA, we evaluated several complex protein-DNA complexes. Several hundred picoseconds of molecular dynamics including solvent and counter-ions was performed to refine our model. Critical hydrogen bonds have been identified and we are testing our hypotheses using site specific mutagenesis.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001081-24
Application #
6456710
Study Section
Project Start
2001-07-01
Project End
2003-08-31
Budget Start
Budget End
Support Year
24
Fiscal Year
2001
Total Cost
$273,230
Indirect Cost
Name
University of California San Francisco
Department
Type
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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