Oligonucleotide Binding to Non-B-DNA in MYC

• Published in: Molecules (Basel, Switzerland) Vol. 24; no. 5; p. 1000
• Main Authors: Umek, Tea, Sollander, Karin, Bergquist, Helen, Wengel, Jesper, Lundin, Karin E, Smith, C I Edvard, Zain, Rula
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 2019; MDPI
• Subjects: anti-gene oligonucleotide; Burkitt's lymphoma; c-Myc protein; Deoxyribonucleic acid; Deregulation; DNA; DNA structure; Electrophoretic mobility; G-quadruplex; Genes; H-DNA; Hydrogen bonds; Lymphoma; Medicin och hälsovetenskap; MYC; Myc protein; non-B-DNA; Nucleotide sequence; Physiology; Plasmids; Proteins; Subgroups; Translocation; anti-gene oligonucleotide; non-B-DNA; MYC; H-DNA; G-quadruplex
• ISSN: 1420-3049; 1431-5157; 1420-3049
• DOI: 10.3390/molecules24051000

, originally named c- , is an oncogene deregulated in many different forms of cancer. Translocation of the 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 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. 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 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 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.