2. Academic Validation
  3. Oligonucleotide Binding to Non-B-DNA in MYC

Oligonucleotide Binding to Non-B-DNA in MYC

  • Molecules. 2019 Mar 12;24(5):1000. doi: 10.3390/molecules24051000.
Tea Umek 1,  Karin Sollander 2,  Helen Bergquist 3,  Jesper Wengel 4,  Karin E Lundin 5,  C I Edvard Smith 6,  Rula Zain 7 8
Affiliations

Affiliations

  • 1 Department of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Huddinge, Sweden. tea.umek@ki.se.
  • 2 Department of Molecular Biology and Functional Genomics, Stockholm University, 171 65 Stockholm, Sweden. karin.sollander@scilifelab.se.
  • 3 Department of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Huddinge, Sweden. hebe7619@gmail.com.
  • 4 Biomolecular Nanoscale Engineerng Center, Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, M5230 Odense, Denmark. jwe@sdu.dk.
  • 5 Department of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Huddinge, Sweden. karin.lundin@ki.se.
  • 6 Department of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Huddinge, Sweden. edvard.smith@ki.se.
  • 7 Department of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Huddinge, Sweden. rula.zain@ki.se.
  • 8 Department of Clinical Genetics, Centre for Rare Diseases, Karolinska University Hospital, SE-171 76 Stockholm, Sweden. rula.zain@ki.se.
PMID: 30871121 DOI: 10.3390/molecules24051000
Abstract

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 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 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.

Keywords

G-quadruplex; H-DNA; MYC; anti-gene oligonucleotide; non-B-DNA.

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