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Molecular flip-flops formed by overlapping Fis sites
Paul N Hengen1, Ilya G Lyakhov, Lisa E Stewart
1Intramural Research Support Program, SAIC, NCI Frederick, Frederick, MD 21702-1201, USA.
Nucleic Acids Research
|November 7, 2003
Summary
The DNA-binding protein Fis protein uses specific site pairings, forming a molecular flip-flop. This structure in E. coli replication origins could control DNA replication or serve as a basis for molecular computing.
Area of Science:
- Molecular Biology
- Genetics
- Biophysics
Background:
- The DNA-binding protein Fis (Factor for Inversion Stimulation) is crucial in bacterial DNA processes.
- Fis often interacts with pairs of DNA-binding sites separated by 7 or 11 base pairs (bp).
- The Escherichia coli chromosomal replication origin contains two overlapping Fis sites with an 11 bp separation.
Purpose of the Study:
- To investigate the functional implications of the 11 bp separated, overlapping Fis sites at the E. coli replication origin.
- To explore the 'molecular flip-flop' mechanism suggested by the binding behavior of Fis.
- To assess the potential of this molecular flip-flop for novel applications in molecular computing.
Main Methods:
- Analysis of DNA-binding protein Fis interactions.
- Structural analysis of Fis binding sites.
- Functional studies related to DNA replication initiation.
Main Results:
- Only one of the two overlapping Fis sites is bound by Fis at any given time, creating a molecular flip-flop.
- This flip-flop mechanism could direct the initiation of replication complexes in alternative directions.
- The precise switching states achievable by this mechanism suggest potential applications.
Conclusions:
- The overlapping Fis sites at the E. coli replication origin function as a molecular flip-flop.
- This flip-flop mechanism may regulate DNA replication initiation.
- Molecular flip-flops represent a promising foundation for developing novel molecular computers.