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Eukaryotic Cell, April 2004, p. 277-287, Vol. 3, No. 2
1535-9778/04/$08.00+0     DOI: 10.1128/EC.3.2.277-287.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Redox Potential Regulates Binding of Universal Minicircle Sequence Binding Protein at the Kinetoplast DNA Replication Origin

Itay Onn,1,2 Neta Milman-Shtepel,1 and Joseph Shlomai1*

Department of Parasitology, The Kuvin Center for the Study of Infectious and Tropical Diseases,1 Department of Molecular Genetics and Biotechnology, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel2

Received 26 October 2003/ Accepted 19 December 2003

Kinetoplast DNA, the mitochondrial DNA of the trypanosomatid Crithidia fasciculata, is a remarkable structure containing 5,000 topologically linked DNA minicircles. Their replication is initiated at two conserved sequences, a dodecamer, known as the universal minicircle sequence (UMS), and a hexamer, which are located at the replication origins of the minicircle L- and H-strands, respectively. A UMS-binding protein (UMSBP), binds specifically the conserved origin sequences in their single stranded conformation. The five CCHC-type zinc knuckle motifs, predicted in UMSBP, fold into zinc-dependent structures capable of binding a single-stranded nucleic acid ligand. Zinc knuckles that are involved in the binding of DNA differ from those mediating protein-protein interactions that lead to the dimerization of UMSBP. Both UMSBP DNA binding and its dimerization are sensitive to redox potential. Oxidation of UMSBP results in the protein dimerization, mediated through its N-terminal domain, with a concomitant inhibition of its DNA-binding activity. UMSBP reduction yields monomers that are active in the binding of DNA through the protein C-terminal region. C. fasciculata trypanothione-dependent tryparedoxin activates the binding of UMSBP to UMS DNA in vitro. The possibility that UMSBP binding at the minicircle replication origin is regulated in vivo by a redox potential-based mechanism is discussed.

* Corresponding author. Mailing address: Department of Parasitology, The Kuvin Center for the Study of Infectious and Tropical Diseases, The Hebrew University-Hadassah Medical School, Ein Karem, Jerusalem 91120, Israel. Phone: 972-2-6758089. Fax: 972-2-6757425. E-mail: Shlomai{at}cc.huji.ac.il.

Eukaryotic Cell, April 2004, p. 277-287, Vol. 3, No. 2
1535-9778/04/$08.00+0     DOI: 10.1128/EC.3.2.277-287.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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