The role of supercoiling in transcriptional control of MYC and its importance in molecular therapeutics

Tracy A. Brooks; Laurence H. Hurley

doi:10.1038/nrc2733

The role of supercoiling in transcriptional control of MYC and its importance in molecular therapeutics

Tracy A. Brooks, Laurence H. Hurley

Pharmacology and Toxicology

Research output: Contribution to journal › Review article › peer-review

258 Scopus citations

Abstract

MYC is deregulated in most tumour types, but an effective means to selectively target its aberrant expression is not yet available. Supercoiling that is induced by transcription has been demonstrated to have dynamic effects on DNA in the MYC promoter element: it converts duplex DNA to non-duplex DNA structures, even at considerable distances from the transcriptional start site. These non-duplex DNA structures, which control both turning on and off of transcription and the rate of transcription firing, are amenable to small-molecule targeting. This dynamic system provides a unique opportunity for the treatment of tumours in which MYC is an important oncogene.

Original language	English (US)
Pages (from-to)	849-861
Number of pages	13
Journal	Nature Reviews Cancer
Volume	9
Issue number	12
DOIs	https://doi.org/10.1038/nrc2733
State	Published - Dec 2009

ASJC Scopus subject areas

Oncology
Cancer Research

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title = "The role of supercoiling in transcriptional control of MYC and its importance in molecular therapeutics",

abstract = "MYC is deregulated in most tumour types, but an effective means to selectively target its aberrant expression is not yet available. Supercoiling that is induced by transcription has been demonstrated to have dynamic effects on DNA in the MYC promoter element: it converts duplex DNA to non-duplex DNA structures, even at considerable distances from the transcriptional start site. These non-duplex DNA structures, which control both turning on and off of transcription and the rate of transcription firing, are amenable to small-molecule targeting. This dynamic system provides a unique opportunity for the treatment of tumours in which MYC is an important oncogene.",

author = "Brooks, {Tracy A.} and Hurley, {Laurence H.}",

note = "Funding Information: This research has been supported by grants from the US National Institutes of Health (CA95060, GM085585 and CA122952) and the Leukemia & Lymphoma Society (6225-08). We are grateful to D. Bishop for help with the manuscript.",

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AU - Hurley, Laurence H.

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N2 - MYC is deregulated in most tumour types, but an effective means to selectively target its aberrant expression is not yet available. Supercoiling that is induced by transcription has been demonstrated to have dynamic effects on DNA in the MYC promoter element: it converts duplex DNA to non-duplex DNA structures, even at considerable distances from the transcriptional start site. These non-duplex DNA structures, which control both turning on and off of transcription and the rate of transcription firing, are amenable to small-molecule targeting. This dynamic system provides a unique opportunity for the treatment of tumours in which MYC is an important oncogene.

AB - MYC is deregulated in most tumour types, but an effective means to selectively target its aberrant expression is not yet available. Supercoiling that is induced by transcription has been demonstrated to have dynamic effects on DNA in the MYC promoter element: it converts duplex DNA to non-duplex DNA structures, even at considerable distances from the transcriptional start site. These non-duplex DNA structures, which control both turning on and off of transcription and the rate of transcription firing, are amenable to small-molecule targeting. This dynamic system provides a unique opportunity for the treatment of tumours in which MYC is an important oncogene.

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The role of supercoiling in transcriptional control of MYC and its importance in molecular therapeutics

Abstract

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