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Topoisomerase 1 inhibits MYC promoter activity by inducing G-quadruplex formation

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

Standard

Topoisomerase 1 inhibits MYC promoter activity by inducing G-quadruplex formation. / Keller, Josephine Geertsen; Hymøller, Kirstine Mejlstrup; Thorsager, Maria Eriksen et al.
I: Nucleic Acids Research, Bind 50, Nr. 11, 06.2022, s. 6332-6342.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

Harvard

Keller, JG, Hymøller, KM, Thorsager, ME, Hansen, NY, Erlandsen, JU, Tesauro, C, Simonsen, AKW, Andersen, AB, Vandsø Petersen, K, Holm, LL, Stougaard, M, Andresen, BS, Kristensen, P, Frøhlich, R & Knudsen, BR 2022, 'Topoisomerase 1 inhibits MYC promoter activity by inducing G-quadruplex formation', Nucleic Acids Research, bind 50, nr. 11, s. 6332-6342. https://doi.org/10.1093/nar/gkac482

APA

Keller, J. G., Hymøller, K. M., Thorsager, M. E., Hansen, N. Y., Erlandsen, J. U., Tesauro, C., Simonsen, A. K. W., Andersen, A. B., Vandsø Petersen, K., Holm, L. L., Stougaard, M., Andresen, B. S., Kristensen, P., Frøhlich, R., & Knudsen, B. R. (2022). Topoisomerase 1 inhibits MYC promoter activity by inducing G-quadruplex formation. Nucleic Acids Research, 50(11), 6332-6342. https://doi.org/10.1093/nar/gkac482

CBE

Keller JG, Hymøller KM, Thorsager ME, Hansen NY, Erlandsen JU, Tesauro C, Simonsen AKW, Andersen AB, Vandsø Petersen K, Holm LL, et al. 2022. Topoisomerase 1 inhibits MYC promoter activity by inducing G-quadruplex formation. Nucleic Acids Research. 50(11):6332-6342. https://doi.org/10.1093/nar/gkac482

MLA

Keller, Josephine Geertsen et al. "Topoisomerase 1 inhibits MYC promoter activity by inducing G-quadruplex formation". Nucleic Acids Research. 2022, 50(11). 6332-6342. https://doi.org/10.1093/nar/gkac482

Vancouver

Keller JG, Hymøller KM, Thorsager ME, Hansen NY, Erlandsen JU, Tesauro C et al. Topoisomerase 1 inhibits MYC promoter activity by inducing G-quadruplex formation. Nucleic Acids Research. 2022 jun.;50(11):6332-6342. doi: 10.1093/nar/gkac482

Author

Keller, Josephine Geertsen ; Hymøller, Kirstine Mejlstrup ; Thorsager, Maria Eriksen et al. / Topoisomerase 1 inhibits MYC promoter activity by inducing G-quadruplex formation. I: Nucleic Acids Research. 2022 ; Bind 50, Nr. 11. s. 6332-6342.

Bibtex

@article{fb162675de9a4c049b99eb71e78923d5,
title = "Topoisomerase 1 inhibits MYC promoter activity by inducing G-quadruplex formation",
abstract = "We have investigated the function of human topoisomerase 1 (TOP1) in regulation of G-quadruplex (G4) formation in the Pu27 region of the MYC P1 promoter. Pu27 is among the best characterized G4 forming sequences in the human genome and it is well known that promoter activity is inhibited upon G4 formation in this region. We found that TOP1 downregulation stimulated transcription from a promoter with wildtype Pu27 but not if the G4 motif in Pu27 was interrupted by mutation(s). The effect was not specific to the MYC promoter and similar results were obtained for the G4 forming promoter element WT21. The other major DNA topoisomerases with relaxation activity, topoisomerases 2α and β, on the other hand, did not affect G4 dependent promoter activity. The cellular studies were supported by in vitro investigations demonstrating a high affinity of TOP1 for wildtype Pu27 but not for mutant sequences unable to form G4. Moreover, TOP1 was able to induce G4 formation in Pu27 inserted in double stranded plasmid DNA in vitro. This is the first time TOP1 has been demonstrated capable of inducing G4 formation in double stranded DNA and of influencing G4 formation in cells.",
author = "Keller, {Josephine Geertsen} and Hym{\o}ller, {Kirstine Mejlstrup} and Thorsager, {Maria Eriksen} and Hansen, {Noriko Y.} and Erlandsen, {Jens Uldum} and Cinzia Tesauro and Simonsen, {Anne Katrine W.} and Andersen, {Anne Bech} and {Vands{\o} Petersen}, Kamilla and Holm, {Lise Lolle} and Magnus Stougaard and Andresen, {Brage Storstein} and Peter Kristensen and Rikke Fr{\o}hlich and Knudsen, {Birgitta R.}",
year = "2022",
month = jun,
doi = "10.1093/nar/gkac482",
language = "English",
volume = "50",
pages = "6332--6342",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "11",

}

RIS

TY - JOUR

T1 - Topoisomerase 1 inhibits MYC promoter activity by inducing G-quadruplex formation

AU - Keller, Josephine Geertsen

AU - Hymøller, Kirstine Mejlstrup

AU - Thorsager, Maria Eriksen

AU - Hansen, Noriko Y.

AU - Erlandsen, Jens Uldum

AU - Tesauro, Cinzia

AU - Simonsen, Anne Katrine W.

AU - Andersen, Anne Bech

AU - Vandsø Petersen, Kamilla

AU - Holm, Lise Lolle

AU - Stougaard, Magnus

AU - Andresen, Brage Storstein

AU - Kristensen, Peter

AU - Frøhlich, Rikke

AU - Knudsen, Birgitta R.

PY - 2022/6

Y1 - 2022/6

N2 - We have investigated the function of human topoisomerase 1 (TOP1) in regulation of G-quadruplex (G4) formation in the Pu27 region of the MYC P1 promoter. Pu27 is among the best characterized G4 forming sequences in the human genome and it is well known that promoter activity is inhibited upon G4 formation in this region. We found that TOP1 downregulation stimulated transcription from a promoter with wildtype Pu27 but not if the G4 motif in Pu27 was interrupted by mutation(s). The effect was not specific to the MYC promoter and similar results were obtained for the G4 forming promoter element WT21. The other major DNA topoisomerases with relaxation activity, topoisomerases 2α and β, on the other hand, did not affect G4 dependent promoter activity. The cellular studies were supported by in vitro investigations demonstrating a high affinity of TOP1 for wildtype Pu27 but not for mutant sequences unable to form G4. Moreover, TOP1 was able to induce G4 formation in Pu27 inserted in double stranded plasmid DNA in vitro. This is the first time TOP1 has been demonstrated capable of inducing G4 formation in double stranded DNA and of influencing G4 formation in cells.

AB - We have investigated the function of human topoisomerase 1 (TOP1) in regulation of G-quadruplex (G4) formation in the Pu27 region of the MYC P1 promoter. Pu27 is among the best characterized G4 forming sequences in the human genome and it is well known that promoter activity is inhibited upon G4 formation in this region. We found that TOP1 downregulation stimulated transcription from a promoter with wildtype Pu27 but not if the G4 motif in Pu27 was interrupted by mutation(s). The effect was not specific to the MYC promoter and similar results were obtained for the G4 forming promoter element WT21. The other major DNA topoisomerases with relaxation activity, topoisomerases 2α and β, on the other hand, did not affect G4 dependent promoter activity. The cellular studies were supported by in vitro investigations demonstrating a high affinity of TOP1 for wildtype Pu27 but not for mutant sequences unable to form G4. Moreover, TOP1 was able to induce G4 formation in Pu27 inserted in double stranded plasmid DNA in vitro. This is the first time TOP1 has been demonstrated capable of inducing G4 formation in double stranded DNA and of influencing G4 formation in cells.

UR - http://www.scopus.com/inward/record.url?scp=85136021085&partnerID=8YFLogxK

U2 - 10.1093/nar/gkac482

DO - 10.1093/nar/gkac482

M3 - Journal article

C2 - 35687110

AN - SCOPUS:85136021085

VL - 50

SP - 6332

EP - 6342

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 11

ER -