DNA G-Quadruplex and i-Motif Structure Formation Is Interdependent in Human Cells

King, Jessica J.; Irving, Kelly L.; Evans, Cameron W.; Chikhale, Rupesh; Becker, Rouven; Morris, C J; Martinez, Cristian David Peña; Schofield, Peter; Christ, Daniel; Hurley, Laurence H.; Waller, Zoë A. E.; Iyer, K. Swaminathan; Smith, Nicole M.

doi:10.1021/jacs.0c11708

Cited by 86 publications

(84 citation statements)

References 21 publications

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“…Occasionally, due to their different formation requirements or the offset position of the respective C-and G-rich sequences, both structures can form simultaneously [163]. In support of mutual exclusivity, a recent study from the Smith group demonstrates that the formation of one structure destabilizes the structure on the complementary strand [164]. Since G4s and i-motifs appear to have distinct roles in transcriptional regulation, it is reasonable that their formation within the same promoter is interdependent.…”

Section: Discussionmentioning

confidence: 99%

The i-Motif as a Molecular Target: More Than a Complementary DNA Secondary Structure

Brown

Kendrick

2021

Pharmaceuticals

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Stretches of cytosine-rich DNA are capable of adopting a dynamic secondary structure, the i-motif. When within promoter regions, the i-motif has the potential to act as a molecular switch for controlling gene expression. However, i-motif structures in genomic areas of repetitive nucleotide sequences may play a role in facilitating or hindering expansion of these DNA elements. Despite research on the i-motif trailing behind the complementary G-quadruplex structure, recent discoveries including the identification of a specific i-motif antibody are pushing this field forward. This perspective reviews initial and current work characterizing the i-motif and providing insight into the biological function of this DNA structure, with a focus on how the i-motif can serve as a molecular target for developing new therapeutic approaches to modulate gene expression and extension of repetitive DNA.

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Section: Discussionmentioning

confidence: 99%

The i-Motif as a Molecular Target: More Than a Complementary DNA Secondary Structure

Brown

Kendrick

2021

Pharmaceuticals

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“…hnRNP E1 binds to i-motifs formed by poly-C tracts, maintains i-motifs, and suppresses G4s in the cell. Recently it has been observed that i-motifs and G4s are mutually exclusive ( King et al, 2020 ). G4s can inhibit DNA replication, but various proteins including helicases, Fen1, and hnRNPs resolve such structures.…”

Section: Discussionmentioning

confidence: 99%

Heterogeneous nuclear ribonucleoprotein E1 binds polycytosine DNA and monitors genome integrity

et al. 2021

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Heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) is a tumor suppressor protein that binds site- and structure-specifically to RNA sequences to regulate mRNA stability, facilitate alternative splicing, and suppress protein translation on several metastasis-associated mRNAs. Here, we show that hnRNP E1 binds polycytosine-rich DNA tracts present throughout the genome, including those at promoters of several oncogenes and telomeres and monitors genome integrity. It binds DNA in a site- and structure-specific manner. hnRNP E1-knockdown cells displayed increased DNA damage signals including γ-H2AX at its binding sites and also showed increased mutations. UV and hydroxyurea treatment of hnRNP E1-knockdown cells exacerbated the basal DNA damage signals with increased cell cycle arrest, activation of checkpoint proteins, and monoubiquitination of proliferating cell nuclear antigen despite no changes in deubiquitinating enzymes. DNA damage caused by genotoxin treatment localized to hnRNP E1 binding sites. Our work suggests that hnRNP E1 facilitates functions of DNA integrity proteins at polycytosine tracts and monitors DNA integrity at these sites.

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“…Also, it is now clear that non-B-DNA structures are powerful determinants of mutagenesis [106]. There are an abundance of non-B-DNA structures [36], but those that are particularly relevant to gene promoter regions are G-quadruplexes [46,47], i-motifs [65,66], cruciforms [69], triplexes [107], and Z-DNA [108], as illustrated in Figure I. These local non-B-DNA structures are often targets of protein binding, including various transcription factors [109][110][111].…”

Section: Box 2 Non-b-dna Structuresmentioning

confidence: 99%

Evolution of Diverse Strategies for Promoter Regulation

2021

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DNA G-Quadruplex and i-Motif Structure Formation Is Interdependent in Human Cells

Cited by 86 publications

References 21 publications

The i-Motif as a Molecular Target: More Than a Complementary DNA Secondary Structure

The i-Motif as a Molecular Target: More Than a Complementary DNA Secondary Structure

Heterogeneous nuclear ribonucleoprotein E1 binds polycytosine DNA and monitors genome integrity

Evolution of Diverse Strategies for Promoter Regulation

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