Open Access

Proceedings of the National Academy of Sciences (PNAS)

Proceedings of the National Academy of Sciences of the United States of America

, volume 116 , issue 41 , pages 20453-20461

DDX5 helicase resolves G-quadruplex and is involved in MYC gene transcriptional activation

Guan-Hui Wu ¹

Xing Zheng ²

Elizabeth Tran ^{2, 3}

Danzhou Yang ^{1, 3, 4}

Hide authors affiliations Show authors affiliations: 4 affiliations

Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, IN 47907; |

Department of Biochemistry, Purdue University, West Lafayette, IN 47907; |

Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN 47906; |

⁴

Purdue Institute for Drug Discovery, Purdue University, West Lafayette, IN 47907 |

Publication type: Journal Article

Publication date: 2019-09-23

Proceedings of the National Academy of Sciences (PNAS)

Proceedings of the National Academy of Sciences of the United States of America

scimago Q1

wos Q1

SJR: 3.414

CiteScore: 16.5

Impact factor: 9.1

ISSN: 00278424, 10916490

DOI: 10.1073/pnas.1909047116

Copy DOI

PubMed ID: 31548374

Multidisciplinary

Abstract

Significance

G-quadruplexes (G4) are 4-stranded nucleic acid secondary structures. MYC is a critical oncogene with a G4 in its promoter (MycG4), which acts as a transcription silencer. MycG4 is very stable and the pathological activation of MYC in cancers requires its active unfolding. We reveal herein that DDX5, a founding member of the DEAD-box RNA helicase family, can unfold DNA G4s. The unfolding mechanism of DDX5 is distinct from previously characterized G4 helicases. Importantly, DDX5 activates MYC gene transcription by proficiently unfolding the promoter MycG4. DDX5 is overexpressed in cancers and the DDX5–MycG4 interaction can be inhibited by small molecules to downregulate MYC . Therefore, our results suggest a new molecular target to suppress MYC for cancer intervention.

Found

1 citation

Beloglazkina Elena

DSc in Chemistry, professor

297 publications, 3 268 citations, 11 reviews

h-index: 29

Lomonosov Moscow State University

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112

Cite this

GOST |

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GOST Copy

Wu G. et al. DDX5 helicase resolves G-quadruplex and is involved in MYC gene transcriptional activation // Proceedings of the National Academy of Sciences of the United States of America. 2019. Vol. 116. No. 41. pp. 20453-20461.

GOST all authors (up to 50) Copy

Wu G., Zheng X., Tran E., Yang D. DDX5 helicase resolves G-quadruplex and is involved in MYC gene transcriptional activation // Proceedings of the National Academy of Sciences of the United States of America. 2019. Vol. 116. No. 41. pp. 20453-20461.

RIS |

Cite this

RIS Copy

TY - JOUR

DO - 10.1073/pnas.1909047116

UR - https://doi.org/10.1073/pnas.1909047116

TI - DDX5 helicase resolves G-quadruplex and is involved in MYC gene transcriptional activation

T2 - Proceedings of the National Academy of Sciences of the United States of America

AU - Wu, Guan-Hui

AU - Zheng, Xing

AU - Tran, Elizabeth

AU - Yang, Danzhou

PY - 2019

DA - 2019/09/23

PB - Proceedings of the National Academy of Sciences (PNAS)

SP - 20453-20461

IS - 41

VL - 116

PMID - 31548374

SN - 0027-8424

SN - 1091-6490

ER -

BibTex |

Cite this

BibTex (up to 50 authors) Copy

@article{2019_Wu,

author = {Guan-Hui Wu and Xing Zheng and Elizabeth Tran and Danzhou Yang},

title = {DDX5 helicase resolves G-quadruplex and is involved in MYC gene transcriptional activation},

journal = {Proceedings of the National Academy of Sciences of the United States of America},

year = {2019},

volume = {116},

publisher = {Proceedings of the National Academy of Sciences (PNAS)},

month = {sep},

url = {https://doi.org/10.1073/pnas.1909047116},

number = {41},

pages = {20453--20461},

doi = {10.1073/pnas.1909047116}

}

MLA

Cite this

MLA Copy

Wu, Guan-Hui, et al. “DDX5 helicase resolves G-quadruplex and is involved in MYC gene transcriptional activation.” Proceedings of the National Academy of Sciences of the United States of America, vol. 116, no. 41, Sep. 2019, pp. 20453-20461. https://doi.org/10.1073/pnas.1909047116.

Publisher

Proceedings of the National Academy of Sciences (PNAS)

Journal

Proceedings of the National Academy of Sciences of the United States of America

scimago Q1

wos Q1

SJR

3.414

CiteScore

16.5

Impact factor

9.1

ISSN

00278424 (Print)

10916490 (Electronic)