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

Guanhui Wu, Zheng Xing, Elizabeth J. Tran, Danzhou Yang

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

G-quadruplexes (G4) are noncanonical secondary structures formed in guanine-rich DNA and RNA sequences. MYC, one of the most critical oncogenes, forms a DNA G4 in its proximal promoter region (MycG4) that functions as a transcriptional silencer. However, MycG4 is highly stable in vitro and its regulatory role would require active unfolding. Here we report that DDX5, one of the founding members of the DEAD-box RNA helicase family, is extremely proficient at unfolding MycG4-DNA. Our results show that DDX5 is a highly active G4-resolvase that does not require a single-stranded overhang and that ATP hydrolysis is not directly coupled to G4-unfolding of DDX5. The chromatin binding sites of DDX5 are G-rich sequences. In cancer cells, DDX5 is enriched at the MYC promoter and activates MYC transcription. The DDX5 interaction with the MYC promoter and DDX5-mediated MYC activation is inhibited by G4-interactive small molecules. Our results uncover a function of DDX5 in resolving DNA and RNA G4s and suggest a molecular target to suppress MYC for cancer intervention.

Original languageEnglish (US)
Pages (from-to)20453-20461
Number of pages9
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number41
DOIs
Publication statusPublished - Jan 1 2019
Externally publishedYes

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Keywords

  • Cancer drug target
  • DDX5
  • G-quadruplex
  • G4-helicase
  • MYC

ASJC Scopus subject areas

  • General

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