Yeast transcription co-activator Sub1 and its human homolog PC4 preferentially bind to G-quadruplex DNA

Gao, Jun; Zybailov, Boris; Byrd, Alicia K.; Griffin, Wezley C.; Chib, Shubeena; Mackintosh, Samuel G.; Tackett, Alan J.; Raney, Kevin D.

doi:10.1039/c5cc00742a

Cited by 38 publications

(45 citation statements)

References 32 publications

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“…A biotinylated DNA sequence based on a region of the c-MYC promoter that readily forms a stable, parallel quadruplex (18) bound to streptavidin-coupled Dynabeads (25) was incubated with human cell lysate to isolate G4DNA-bound proteins. To account for nonspecific interactions, a single-stranded DNA (ssDNA) was incubated with lysate in a separate experiment.…”

Section: Resultsmentioning

confidence: 99%

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

Byrd¹,

Zybailov

Maddukuri³

et al. 2016

Journal of Biological Chemistry

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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.

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Section: Resultsmentioning

confidence: 99%

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

Byrd¹,

Zybailov

Maddukuri³

et al. 2016

Journal of Biological Chemistry

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“…ScPif1 also interacts with Sub1 [109], a co-transcriptional activator that reduces genome instability at G4DNA sequences in yeast [109]. Sub1 binds tightly to G4DNA but does not unfold G4DNA structures [110]. This suggests that Sub1 may instead recruit a G4DNA resolving protein to the G4DNA site.…”

Section: Unanswered Questionsmentioning

confidence: 99%

Structure and function of Pif1 helicase

Byrd

Raney

2017

Biochemical Society Transactions

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Pif1 family helicases have multiple roles in maintenance of nuclear and mitochondrial DNA in eukaryotes. S. cerevisiae Pif1 is involved in replication through barriers to replication such as G-quadruplexes and protein blocks and reduces genetic instability at these sites. Another Pif1 family helicase in S. cerevisiae, Rrm3, assists in fork progression through replication fork barriers at the rDNA locus and tRNA genes. ScPif1 also negatively regulates telomerase, facilitates Okazaki Fragment processing, and acts with polymerase δ in break induced repair. Recent crystal structures of bacterial Pif1 helicases and the helicase domain of human PIF1 combined with several biochemical and biological studies on the activities of Pif1 helicases have increased our understanding of the function of these proteins. This review article focuses on these structures and the mechanism(s) proposed for Pif1’s various activities on DNA.

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“…Considering that both these compo nents play a major role in coordinating the system of DNA damage identification and reparation mechanisms related to local melting of the double helix, it has been suggested that G4 can regulate these processes. A mechanism of G4 mediated regulation of gene expression and other processes of DNA metabolism has been discussed [312]. This mech anism is based on interaction of DNA G4s with yeast tran scription coactivator Sub1 and its human homolog PC4.…”

Section: Small Molecule Ligands and Proteins Recognizing And Specificmentioning

confidence: 99%

Structure, properties, and biological relevance of the DNA and RNA G-quadruplexes: Overview 50 years after their discovery

Dolinnaya

Ogloblina²,

Yakubovskaya³

2016

Biochemistry Moscow

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G-quadruplexes (G4s), which are known to have important roles in regulation of key biological processes in both normal and pathological cells, are the most actively studied non-canonical structures of nucleic acids. In this review, we summarize the results of studies published in recent years that change significantly scientific views on various aspects of our understanding of quadruplexes. Modern notions on the polymorphism of DNA quadruplexes, on factors affecting thermodynamics and kinetics of G4 folding-unfolding, on structural organization of multiquadruplex systems, and on conformational features of RNA G4s and hybrid DNA-RNA G4s are discussed. Here we report the data on location of G4 sequence motifs in the genomes of eukaryotes, bacteria, and viruses, characterize G4-specific small-molecule ligands and proteins, as well as the mechanisms of their interactions with quadruplexes. New information on the structure and stability of G4s in telomeric DNA and oncogene promoters is discussed as well as proof being provided on the occurrence of G-quadruplexes in cells. Prominence is given to novel experimental techniques (single molecule manipulations, optical and magnetic tweezers, original chemical approaches, G4 detection in situ, in-cell NMR spectroscopy) that facilitate breakthroughs in the investigation of the structure and functions of G-quadruplexes.

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Yeast transcription co-activator Sub1 and its human homolog PC4 preferentially bind to G-quadruplex DNA

Cited by 38 publications

References 32 publications

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

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

Structure and function of Pif1 helicase

Structure, properties, and biological relevance of the DNA and RNA G-quadruplexes: Overview 50 years after their discovery

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