High-throughput sequencing of DNA G-quadruplex structures in the human genome

Chambers, Vicki S.; Marsico, Giovanni; Boutell, Jonathan M.; Antonio, Marco Di; Smith, Geoffrey; Balasubramanian, Shankar

doi:10.1038/nbt.3295

Cited by 1,038 publications

(1,132 citation statements)

References 32 publications

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“…It is of note that hypersensitive DNA cleavage sites have been described adjacent to G4DNA sequences in mitochondria (52,78,79) and proto-oncogenes (80,81). Recent results from the Balasubramanian laboratory support the conclusion that a very large number of DNA sequences throughout the genome can fold into quadruplex structures in addition to telomeric sequences (82). Hence, nuclear and mitochondrial human DNA has great potential for producing G4DNA during repair or excision of damaged DNA.…”

Section: Discussionmentioning

confidence: 58%

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: Discussionmentioning

confidence: 58%

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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“…S1D; Supplemental Tables 1, 2), possibly due to the GC-rich nature of the mouse L1 3 ′ end sequence (Chambers et al 2015). Furthermore, the de novo L1 insertions had relatively long poly(A) tracts (average ∼64 bp), reducing the likelihood that L1 3 ′ end sequence and flanking genomic DNA would be captured in a single sequencing read.…”

Section: Resultsmentioning

confidence: 99%

Heritable L1 retrotransposition in the mouse primordial germline and early embryo

et al. 2017

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LINE-1 (L1) retrotransposons are a noted source of genetic diversity and disease in mammals. To expand its genomic footprint, L1 must mobilize in cells that will contribute their genetic material to subsequent generations. Heritable L1 insertions may therefore arise in germ cells and in pluripotent embryonic cells, prior to germline specification, yet the frequency and predominant developmental timing of such events remain unclear. Here, we applied mouse retrotransposon capture sequencing (mRC-seq) and whole-genome sequencing (WGS) to pedigrees of C57BL/6J animals, and uncovered an L1 insertion rate of ≥1 event per eight births. We traced heritable L1 insertions to pluripotent embryonic cells and, strikingly, to early primordial germ cells (PGCs). New L1 insertions bore structural hallmarks of target-site primed reverse transcription (TPRT) and mobilized efficiently in a cultured cell retrotransposition assay. Together, our results highlight the rate and evolutionary impact of heritable L1 retrotransposition and reveal retrotransposition-mediated genomic diversification as a fundamental property of pluripotent embryonic cells in vivo.

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“…In addition to telomeric G4s, it was shown using genome sequencing that approximately 700,000 DNA G4-like sequences, 81 while bioinformatic studies reported around 350,000 sequences with the potential to form G4 structures. 82 Finally, immunoprecipitating G4…”

Section: Promoter G4smentioning

confidence: 99%

On the binding modes of metal NHC complexes with DNA secondary structures: implications for therapy and imaging

et al. 2017

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High-throughput sequencing of DNA G-quadruplex structures in the human genome

Cited by 1,038 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

Heritable L1 retrotransposition in the mouse primordial germline and early embryo

On the binding modes of metal NHC complexes with DNA secondary structures: implications for therapy and imaging

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