Oligonucleotide Binding to Non-B-DNA in MYC

Autor: Tea Umek, Karin Sollander, Helen Bergquist, Jesper Wengel, Karin E. Lundin, C.I. Edvard Smith, Rula Zain
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Molecules, Vol 24, Iss 5, p 1000 (2019)
Druh dokumentu: article
ISSN: 1420-3049
DOI: 10.3390/molecules24051000
Popis: 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) [1]. Sporadic BL constitutes one subgroup where one of the translocation sites is located at the 5′-vicinity of the two major MYC promoters P1 and P2. 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[2,3]. 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.
Databáze: Directory of Open Access Journals
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