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J Biol Chem. 2016 Aug 19;291(34):18041-57. doi: 10.1074/jbc.M116.718478. Epub 2016 Jul 1.

Evidence That G-quadruplex DNA Accumulates in the Cytoplasm and Participates in Stress Granule Assembly in Response to Oxidative Stress.

Author information

1
From the Departments of Biochemistry and Molecular Biology and.
2
From the Departments of Biochemistry and Molecular Biology and the University of Arkansas at Little Rock/University of Arkansas for Medical Sciences (UALR/UAMS) Joint Graduate Program in Bioinformatics, University of Arkansas at Little Rock, Little Rock, Arkansas 72204.
3
the University of Arkansas at Little Rock/University of Arkansas for Medical Sciences (UALR/UAMS) Joint Graduate Program in Bioinformatics, University of Arkansas at Little Rock, Little Rock, Arkansas 72204.
4
From the Departments of Biochemistry and Molecular Biology and the Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205 and.
5
the Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205 and Neurobiology and Developmental Sciences and.
6
From the Departments of Biochemistry and Molecular Biology and the Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205 and RaneyKevinD@uams.edu.

Abstract

Cells engage numerous signaling pathways in response to oxidative stress that together repair macromolecular damage or direct the cell toward apoptosis. As a result of DNA damage, mitochondrial DNA or nuclear DNA has been shown to enter the cytoplasm where it binds to "DNA sensors," which in turn initiate signaling cascades. Here we report data that support a novel signaling pathway in response to oxidative stress mediated by specific guanine-rich sequences that can fold into G-quadruplex DNA (G4DNA). In response to oxidative stress, we demonstrate that sequences capable of forming G4DNA appear at increasing levels in the cytoplasm and participate in assembly of stress granules. Identified proteins that bind to endogenous G4DNA in the cytoplasm are known to modulate mRNA translation and participate in stress granule formation. Consistent with these findings, stress granule formation is known to regulate mRNA translation during oxidative stress. We propose a signaling pathway whereby cells can rapidly respond to DNA damage caused by oxidative stress. Guanine-rich sequences that are excised from damaged genomic DNA are proposed to enter the cytoplasm where they can regulate translation through stress granule formation. This newly proposed role for G4DNA provides an additional molecular explanation for why such sequences are prevalent in the human genome.

KEYWORDS:

DNA repair; G-quadruplex; oxidative stress; signaling; stress granule; stress response; telomere

PMID:
27369081
PMCID:
PMC5016190
DOI:
10.1074/jbc.M116.718478
[Indexed for MEDLINE]
Free PMC Article

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