Oligonucleotide binding to non-B-DNA in MYC

Tea Umek, Karin Sollander, Helen Bergquist, Jesper Wengel, Karin E. Lundin, C. I. Edvard Smith, Rula Zain

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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.

Original languageEnglish
Article number1000
JournalMolecules
Volume24
Issue number5
Number of pages11
ISSN1420-3049
DOIs
Publication statusPublished - 12. Mar 2019

Fingerprint

oligonucleotides
Oligonucleotides
genes
strands
Genes
Assays
myc Genes
Electrophoretic Mobility Shift Assay
oncogenes
Electrophoretic mobility
purines
plasmids
subgroups
Immunoglobulins
cleavage
Plasmids
deoxyribonucleic acid
cancer
DNA
shift

Keywords

  • Anti-gene oligonucleotide
  • G-quadruplex
  • H-DNA
  • MYC
  • Non-B-DNA

Cite this

Umek, T., Sollander, K., Bergquist, H., Wengel, J., Lundin, K. E., Edvard Smith, C. I., & Zain, R. (2019). Oligonucleotide binding to non-B-DNA in MYC. Molecules, 24(5), [1000]. https://doi.org/10.3390/molecules24051000
Umek, Tea ; Sollander, Karin ; Bergquist, Helen ; Wengel, Jesper ; Lundin, Karin E. ; Edvard Smith, C. I. ; Zain, Rula. / Oligonucleotide binding to non-B-DNA in MYC. In: Molecules. 2019 ; Vol. 24, No. 5.
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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 = "Anti-gene oligonucleotide, G-quadruplex, H-DNA, MYC, Non-B-DNA",
author = "Tea Umek and Karin Sollander and Helen Bergquist and Jesper Wengel and Lundin, {Karin E.} and {Edvard Smith}, {C. I.} and Rula Zain",
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Umek, T, Sollander, K, Bergquist, H, Wengel, J, Lundin, KE, Edvard Smith, CI & Zain, R 2019, 'Oligonucleotide binding to non-B-DNA in MYC', Molecules, vol. 24, no. 5, 1000. https://doi.org/10.3390/molecules24051000

Oligonucleotide binding to non-B-DNA in MYC. / Umek, Tea; Sollander, Karin; Bergquist, Helen; Wengel, Jesper; Lundin, Karin E.; Edvard Smith, C. I.; Zain, Rula.

In: Molecules, Vol. 24, No. 5, 1000, 12.03.2019.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Oligonucleotide binding to non-B-DNA in MYC

AU - Umek, Tea

AU - Sollander, Karin

AU - Bergquist, Helen

AU - Wengel, Jesper

AU - Lundin, Karin E.

AU - Edvard Smith, C. I.

AU - Zain, Rula

PY - 2019/3/12

Y1 - 2019/3/12

N2 - 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.

AB - 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.

KW - Anti-gene oligonucleotide

KW - G-quadruplex

KW - H-DNA

KW - MYC

KW - Non-B-DNA

U2 - 10.3390/molecules24051000

DO - 10.3390/molecules24051000

M3 - Journal article

C2 - 30871121

AN - SCOPUS:85062888218

VL - 24

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 5

M1 - 1000

ER -

Umek T, Sollander K, Bergquist H, Wengel J, Lundin KE, Edvard Smith CI et al. Oligonucleotide binding to non-B-DNA in MYC. Molecules. 2019 Mar 12;24(5). 1000. https://doi.org/10.3390/molecules24051000