The major objective of the proposed research is to understand the interrelationship between the structure and function of a newly identified nuclease human flap endonuclease-1 (FEN-1) in the context of DNA repair. Current biochemical and genetic data have demonstrated that FEN-1 is a structure specific endonuclease. It may play critical roles in DNA replication, repair, and recombination. However, sufficient evidence is not available for this class of nucleases to establish a structural basis for their unique biochemical and physiological functions and their structural and functional relationships. Our preliminary data on the analysis of biochemical domains has suggested that there are three functional domains in human FEN-1 protein responsible for the functions of DNA substrate binding, catalysis, protein-protein interaction, and nuclear localization. The proposed research is designed to establish the detailed structural understanding of the catalytic cen ter for DNA substrate recognition, binding and cleavage. and to analyze the structural elements responsible for protein-protein interaction and nuclear localization. We will examine functional alterations through site-directed mutagenisis of each functional domain. The mutant proteins will be characterized by our newly developed kinetic flow cytometry, biochemical assays and crystallographic structural analysis, and green fluorescence driven microscopy.
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| Ai, Ye; Sanders, Claire K; Marrone, Babetta L (2013) Separation of Escherichia coli bacteria from peripheral blood mononuclear cells using standing surface acoustic waves. Anal Chem 85:9126-34 |
| Sanders, Claire K; Mourant, Judith R (2013) Advantages of full spectrum flow cytometry. J Biomed Opt 18:037004 |
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| Chaudhary, Anu; Ganguly, Kumkum; Cabantous, Stephanie et al. (2012) The Brucella TIR-like protein TcpB interacts with the death domain of MyD88. Biochem Biophys Res Commun 417:299-304 |
| Marina, Oana C; Sanders, Claire K; Mourant, Judith R (2012) Correlating light scattering with internal cellular structures. Biomed Opt Express 3:296-312 |
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| Marina, Oana C; Sanders, Claire K; Mourant, Judith R (2012) Effects of acetic acid on light scattering from cells. J Biomed Opt 17:085002-1 |
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