Identification of novel interactors of human telomeric G-quadruplex DNA

Pagano, Bruno; Margarucci, Luigi; Zizza, Pasquale; Amato, Jussara; Iaccarino, Nunzia; Cassiano, Chiara; Salvati, Erica; Novellino, Ettore; Biroccio, Annamaria; Casapullo, Agostino; Randazzo, Antonio

doi:10.1039/c4cc07231f

Cited by 34 publications

(34 citation statements)

References 37 publications

(21 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Indeed, many natural proteins have been identified that interact with G4s (see G4 Interacting Proteins Database, http://bsbe.iiti.ac.in/bsbe/ipdb/) [61]. The identification of G4 associated proteins has mostly relied on affinity proteomics experiments employing RNA and DNA G4 oligomers as baits to isolate G4 interactors from cellular extracts [62][63][64][65]. Other approaches involve computational analysis of genomic protein binding sites to assess the enrichment of predicted G4 motifs within these binding sites [54,66], or meta-analysis, in which shared structural features of G4-binding protein domains were compared to predict new putative G4 interactors [67,68].…”

Section: Natural G4-binding Proteinsmentioning

confidence: 99%

“…In accordance with the G4 forming potential of the telomere repeat sequence, many telomere-associated proteins have been shown to interact with G4 structures [63]. For instance, POT1 [75] and RPA [76], two components of the shelterin complex, as well as the human CST complex [77], are able to bind and unwind telomeric G4 structures and assist the action of telomerase.…”

Section: Natural G4-binding Proteinsmentioning

confidence: 99%

See 1 more Smart Citation

The Structure and Function of DNA G-Quadruplexes

Spiegel

Adhikari

Balasubramanian

2020

Trends in Chemistry

590

568

View full text Add to dashboard Cite

Guanine-rich DNA sequences can fold into four-stranded, noncanonical secondary structures called G-quadruplexes (G4s). G4s were initially considered a structural curiosity, but recent evidence suggests their involvement in key genome functions such as transcription, replication, genome stability, and epigenetic regulation, together with numerous connections to cancer biology. Collectively, these advances have stimulated research probing G4 mechanisms and consequent opportunities for therapeutic intervention. Here, we provide a perspective on the structure and function of G4s with an emphasis on key molecules and methodological advances that enable the study of G4 structures in human cells. We also critically examine recent mechanistic insights into G4 biology and protein interaction partners and highlight opportunities for drug discovery. Beyond the DNA Double HelixA chemist's perspective on the function of a molecule, or a system of molecules, is typically led by a consideration of how molecular structure dictates function. The most widely recognised DNA structure is that of the classical DNA double helix [1], which defines a structural basis for the genetic code via defined base-pairing. Yet, it is evident that DNA is structurally dynamic and capable of adopting alternative secondary structures. One such class of DNA secondary structure is the four-stranded Gquadruplex (G4). Herein, we discuss some of the key scientific history that has shaped our understanding of this structural motif, its probable functions in biology, and major unanswered questions that remain to be solved.

show abstract

Section: Natural G4-binding Proteinsmentioning

confidence: 99%

Section: Natural G4-binding Proteinsmentioning

confidence: 99%

The Structure and Function of DNA G-Quadruplexes

Spiegel

Adhikari

Balasubramanian

2020

Trends in Chemistry

590

568

View full text Add to dashboard Cite

show abstract

“…HMGB1 binding with the linker region of nucleosomal DNA destabilizes the nucleosome structure (presumably due to DNA bending) and thus promotes nucleosome sliding and remodeling . HMGB1 has been identified as a binding partner of telomeric G4 in a pull‐down assay and the initial in vitro comparative studies with promoter G4s confirmed HMGB1 selectivity for the telomeric quadruplex structure . However, subsequent studies revealed that HMGB1 also has a high affinity for the KRAS promoter G4 .…”

Section: G4s Might Directly Engage Architectural Chromatin Proteins mentioning

confidence: 99%

DNA G‐Quadruplexes (G4s) Modulate Epigenetic (Re)Programming and Chromatin Remodeling

2019

View full text Add to dashboard Cite

Here, the emerging data on DNA G‐quadruplexes (G4s) as epigenetic modulators are reviewed and integrated. This concept has appeared and evolved substantially in recent years. First, persistent G4s (e.g., those stabilized by exogenous ligands) were linked to the loss of the histone code. More recently, transient G4s (i.e., those formed upon replication or transcription and unfolded rapidly by helicases) were implicated in CpG island methylation maintenance and de novo CpG methylation control. The most recent data indicate that there are direct interactions between G4s and chromatin remodeling factors. Finally, multiple findings support the indirect participation of G4s in chromatin reshaping via interactions with remodeling‐related transcription factors (TFs) or damage responders. Here, the links between the above processes are analyzed; also, how further elucidation of these processes may stimulate the progress of epigenetic therapy is discussed, and the remaining open questions are highlighted.

show abstract

“…In conclusion, we have described the synthesis of an ew chiral ligand (R/S)-L with ap yridine donor and ag lycol backbone,w hich can be incorporated internally into oligonucleotide strands.I naunimolecular human telomeric G-quadruplex, one G-tetrad can be replaced by four such ligands that are preorganized to coordinate to ac opper ion, thus stabilizing the structure.U sing the metal-base tetrad within a Tetrahymena telomeric G-quadruplex enables the switching of topologies from ah ybrid-dominated conformer mixture to an antiparallel strand arrangement, as confirmed by UV melting curves and CD analysis.T he incorporation of four pyridine ligands into the 15mer thrombin-binding aptamer permits copper-triggered control over thrombincatalyzed fibrinogen hydrolysis,asdemonstrated by aclotting assay.S witchable G-quadruplex folding may be of value in protein affinity assays, [10,31] where paramagnetic metal ions will enable EPR-based readout. In addition, we are currently extending this concept to systems containing other metals and ligands.T he herein introduced incorporation of several ligands into as ingle-stranded G-quadruplex allows for heteroleptic ligand combinations aimed at biohybrid coordination environments with tunable catalytic functions and redox properties.…”

Section: Communicationsmentioning

confidence: 99%

Copper‐Induced Topology Switching and Thrombin Inhibition with Telomeric DNA G‐Quadruplexes

2017

View full text Add to dashboard Cite

The topological diversity of DNA G-quadruplexes may play a crucial role in its biological function. Reversible control over a specific folding topology was achieved by the synthesis of a chiral, glycol-based pyridine ligand and its fourfold incorporation into human telomeric DNA by solid-phase synthesis. Square-planar coordination to a Cu ion led to the formation of a highly stabilizing intramolecular metal-base tetrad, substituting one G-tetrad in the parent unimolecular G-quadruplex. For the Tetrahymena telomeric repeat, Cu -triggered switching from a hybrid-dominated conformer mixture to an antiparallel topology was observed. Cu -dependent control over a protein-G-quadruplex interaction was shown for the thrombin-tba pair (tba=thrombin-binding aptamer).

show abstract

Identification of novel interactors of human telomeric G-quadruplex DNA

Cited by 34 publications

References 37 publications

The Structure and Function of DNA G-Quadruplexes

The Structure and Function of DNA G-Quadruplexes

DNA G‐Quadruplexes (G4s) Modulate Epigenetic (Re)Programming and Chromatin Remodeling

Copper‐Induced Topology Switching and Thrombin Inhibition with Telomeric DNA G‐Quadruplexes

Contact Info

Product

Resources

About