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  • 1. Umek, Tea
    et al.
    Sollander, Karin
    Stockholm University, Faculty of Science, Department of Molecular Biology and Functional Genomics.
    Bergquist, Helen
    Wengel, Jesper
    Lundin, Karin E.
    Smith, C. I. Edvard
    Zain, Rula
    Oligonucleotide Binding to Non-B-DNA in MYC2019In: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 24, no 5, article id 1000Article in journal (Refereed)
    Abstract [en]

    MYC, originally named c-myc, is an oncogene deregulated in many different forms of cancer. Translocation of the MYC gene to an immunoglobulin gene leads to an overexpression and the development of Burkitt's lymphoma (BL). Sporadic BL constitutes one subgroup where one of the translocation sites is located at the 5'-vicinity of the two major MYC promoters P-1 and P-2. A non-B-DNA forming sequence within this region has been reported with the ability to form an intramolecular triplex (H-DNA) or a G-quadruplex. We have examined triplex formation at this site first by using a 17 bp triplex-forming oligonucleotide (TFO) and a double strand DNA (dsDNA) target corresponding to the MYC sequence. An antiparallel purine-motif triplex was detected using electrophoretic mobility shift assay. Furthermore, we probed for H-DNA formation using the BQQ-OP based triplex-specific cleavage assay, which indicated the formation of the structure in the supercoiled plasmid containing the corresponding region of the MYC promoter. Targeting non-B-DNA structures has therapeutic potential; therefore, we investigated their influence on strand-invasion of anti-gene oligonucleotides (ON)s. We show that in vitro, non-B-DNA formation at the vicinity of the ON target site facilitates dsDNA strand-invasion of the anti-gene ONs.

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