Effects of nucleoside analog incorporation on DNA binding to the DNA binding domain of the GATA-1 erythroid transcription factor

Authors

    Authors

    M. Foti; J. G. Omichinski; S. Stahl; D. Maloney; J. West;B. I. Schweitzer

    Comments

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    Abbreviated Journal Title

    FEBS Lett.

    Keywords

    ganciclovir; cytosine arabinoside; GATA-1; binding; nuclear magnetic; resonance; THYMIDINE KINASE GENE; RESTRAINED MOLECULAR-DYNAMICS; RELAXATION MATRIX; REFINEMENT; BRAIN-TUMORS; IN-VIVO; 9-(1, 3-DIHYDROXY-2-PROPOXYMETHYL)GUANINE TRIPHOSPHATE; 1-BETA-D-ARABINOFURANOSYLCYTOSINE 5'-TRIPHOSPHATE; TRANSPLANT; RECIPIENTS; COLONY FORMATION; NUCLEIC-ACIDS; Biochemistry & Molecular Biology; Biophysics; Cell Biology

    Abstract

    We investigate here the effects of the incorporation of the nucleoside analogs araC (1-beta-D-arabinofuranosylcytosine) and ganciclovir (9-[(1,3-dihydroxy-2-propoxy)methyl] guanine) into the DNA binding recognition sequence for the GATA-1 erythroid transcription factor. A 10-fold decrease in binding affinity was observed for the ganciclovir-substituted DNA complex in comparison to an unmodified DNA of the same sequence composition. AraC substitution did not result in any changes in binding affinity, H-1-N-15 HSQC and NOESY NMR experiments revealed a number of chemical shift changes in both DNA and protein in the ganciclovir-modified DNA-protein complex when compared to the unmodified DNA-protein complex, These changes in chemical shift and binding affinity suggest a change in the binding mode of the complex when ganciclovir is incorporated into the GATA DNA binding site. (C) 1999 Federation of European Biochemical Societies.

    Journal Title

    Febs Letters

    Volume

    444

    Issue/Number

    1

    Publication Date

    1-1-1999

    Document Type

    Article

    Language

    English

    First Page

    47

    Last Page

    53

    WOS Identifier

    WOS:000078616200010

    ISSN

    0014-5793

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