scholarly journals Cover Picture: Light-Induced Formation of G-Quadruplex DNA Secondary Structures (ChemBioChem 11/2005)

ChemBioChem ◽  
2005 ◽  
Vol 6 (11) ◽  
pp. 1913-1913
Author(s):  
Günter Mayer ◽  
Lenz Kröck ◽  
Vera Mikat ◽  
Marianne Engeser ◽  
Alexander Heckel
Keyword(s):  
Secondary Structures ◽  
Quadruplex Dna ◽  
G Quadruplex ◽  
Dna Secondary Structures

scholarly journals Pif1 is essential for efficient replisome progression through lagging strand G-quadruplex DNA secondary structures

2018 ◽  
Vol 46 (22) ◽  
pp. 11847-11857 ◽  
Author(s):  
Danielle Dahan ◽  
Ioannis Tsirkas ◽  
Daniel Dovrat ◽  
Melanie A Sparks ◽  
Saurabh P Singh ◽  
...  
Keyword(s):  
Secondary Structures ◽  
Quadruplex Dna ◽  
G Quadruplex ◽  
Dna Secondary Structures ◽  
Lagging Strand

Light-Induced Formation of G-Quadruplex DNA Secondary Structures

ChemBioChem ◽  
2005 ◽  
Vol 6 (11) ◽  
pp. 1966-1970 ◽  
Author(s):  
Günter Mayer ◽  
Lenz Kröck ◽  
Vera Mikat ◽  
Marianne Engeser ◽  
Alexander Heckel
Keyword(s):  
Secondary Structures ◽  
Quadruplex Dna ◽  
G Quadruplex ◽  
Dna Secondary Structures

scholarly journals Perspectives for Applying G-Quadruplex Structures in Neurobiology and Neuropharmacology

2019 ◽  
Vol 20 (12) ◽  
pp. 2884 ◽  
Author(s):  
Sefan Asamitsu ◽  
Masayuki Takeuchi ◽  
Susumu Ikenoshita ◽  
Yoshiki Imai ◽  
Hirohito Kashiwagi ◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Neurological Diseases ◽  
Secondary Structures ◽  
Neuronal Function ◽  
Double Stranded Rna ◽  
Quadruplex Dna ◽  
Functional Roles ◽  
G Quadruplex ◽  
Dna Secondary Structures

The most common form of DNA is a right-handed helix or the B-form DNA. DNA can also adopt a variety of alternative conformations, non-B-form DNA secondary structures, including the DNA G-quadruplex (DNA-G4). Furthermore, besides stem-loops that yield A-form double-stranded RNA, non-canonical RNA G-quadruplex (RNA-G4) secondary structures are also observed. Recent bioinformatics analysis of the whole-genome and transcriptome obtained using G-quadruplex–specific antibodies and ligands, revealed genomic positions of G-quadruplexes. In addition, accumulating evidence pointed to the existence of these structures under physiologically- and pathologically-relevant conditions, with functional roles in vivo. In this review, we focused on DNA-G4 and RNA-G4, which may have important roles in neuronal function, and reveal mechanisms underlying neurological disorders related to synaptic dysfunction. In addition, we mention the potential of G-quadruplexes as therapeutic targets for neurological diseases.

scholarly journals Covalently Functionalized DNA Duplexes and Quadruplexes as Hybrid Catalysts in an Enantioselective Friedel–Crafts Reaction

Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3121
Author(s):  
Surjendu Dey ◽  
Andres Jäschke
Keyword(s):  
Secondary Structures ◽  
Catalytic Performance ◽  
Dna Duplexes ◽  
Quadruplex Dna ◽  
Hybrid Catalysts ◽  
Modified Dna ◽  
G Quadruplex ◽  
Dna Secondary Structures ◽  
Dna Strand

The precise site-specific positioning of metal–ligand complexes on various DNA structures through covalent linkages has gained importance in the development of hybrid catalysts for aqueous-phase homogeneous catalysis. Covalently modified double-stranded and G-quadruplex DNA-based hybrid catalysts have been investigated separately. To understand the role of different DNA secondary structures in enantioselective Friedel–Crafts alkylation, a well-known G-quadruplex-forming sequence was covalently modified at different positions. The catalytic performance of this modified DNA strand was studied in the presence and absence of a complementary DNA sequence, resulting in the formation of two different secondary structures, namely duplex and G-quadruplex. Indeed, the secondary structures had a tremendous effect on both the yield and stereoselectivity of the catalyzed reaction. In addition, the position of the modification, the topology of the DNA, the nature of the ligand, and the length of the linker between ligand and DNA were found to modulate the catalytic performance of the hybrid catalysts. Using the optimal linker length, the quadruplexes formed the (−)-enantiomer with up to 65% ee, while the duplex yielded the (+)-enantiomer with up to 62% ee. This study unveils a new and simple way to control the stereochemical outcome of a Friedel–Crafts reaction.

scholarly journals Replication of G Quadruplex DNA

Genes ◽  
2019 ◽  
Vol 10 (2) ◽  
pp. 95 ◽  
Author(s):  
Leticia Koch Lerner ◽  
Julian E. Sale
Keyword(s):  
Dna Replication ◽  
Dna Sequences ◽  
Secondary Structures ◽  
Dna Unwinding ◽  
Chromosomal Dna ◽  
Quadruplex Dna ◽  
Epigenetic Instability ◽  
G Quadruplex ◽  
Dna Secondary Structures ◽  
Dna Template

A cursory look at any textbook image of DNA replication might suggest that the complex machine that is the replisome runs smoothly along the chromosomal DNA. However, many DNA sequences can adopt non-B form secondary structures and these have the potential to impede progression of the replisome. A picture is emerging in which the maintenance of processive DNA replication requires the action of a significant number of additional proteins beyond the core replisome to resolve secondary structures in the DNA template. By ensuring that DNA synthesis remains closely coupled to DNA unwinding by the replicative helicase, these factors prevent impediments to the replisome from causing genetic and epigenetic instability. This review considers the circumstances in which DNA forms secondary structures, the potential responses of the eukaryotic replisome to these impediments in the light of recent advances in our understanding of its structure and operation and the mechanisms cells deploy to remove secondary structure from the DNA. To illustrate the principles involved, we focus on one of the best understood DNA secondary structures, G quadruplexes (G4s), and on the helicases that promote their resolution.

scholarly journals A short peptide that preferentially binds c-MYC G-quadruplex DNA

2020 ◽  
Vol 56 (63) ◽  
pp. 8940-8943 ◽  
Author(s):  
Aisling Minard ◽  
Danielle Morgan ◽  
Federica Raguseo ◽  
Anna Di Porzio ◽  
Denise Liano ◽  
...  
Keyword(s):  
Nucleic Acids ◽  
Human Genome ◽  
Promoter Region ◽  
Secondary Structures ◽  
Quadruplex Dna ◽  
Short Peptide ◽  
G Quadruplex

G-quadruplexes are nucleic-acids secondary structures that are highly abundant in the human genome. In this work,we identified a short-peptide that displays selectivity for the G-quadruplex formed in the promoter region of the oncogene c-MYC.

Novel Targeting Of BCL2 and MYC DNA Secondary Structures In Diffuse Large B-Cell Lymphoma (DLBCL)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2532-2532
Author(s):  
Samantha L. Kendrick ◽  
Crystal Loftin ◽  
Xavier Rivera ◽  
Laurence H. Hurley ◽  
Lisa M. Rimsza
Keyword(s):  
Cell Viability ◽  
B Cell ◽  
Small Molecules ◽  
Cell Lines ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Secondary Structures ◽  
G Quadruplex ◽  
Dna Secondary Structures ◽  
Chemotherapy Agents

Abstract Background The most aggressive diffuse large B-cell lymphomas (DLBCL) display concurrent over-expression of the B-cell lymphoma gene-2 (BCL2) and cellular-myelocytomatosis (MYC) oncogenes. DLBCL with these features are nearly uniformly fatal due to the lethal combination of resistance to apoptosis and high proliferation. Currently, there are no effective strategies to treat these patients. We propose directly targeting BCL2/MYC transcription through DNA secondary structures to induce chemosensitization in BCL2/MYC overexpressing DLBCL cell lines. DNA secondary structures are proposed to act as molecular switches, turning gene expression on or off. In support of this, genome-wide analyses have detected DNA secondary structure-forming sequences within close proximity of transcriptional start sites in 43% of promoter regions, which were mostly oncogene promoters including BCL2 and MYC (Huppert et al., Nucleic Acids Res 2007). Directly upstream of the BCL2 and MYC promoters are guanine and cytosine (GC)-rich elements capable of transitioning to G-quadruplex and i-motif secondary structures, respectively. Previous high-throughput fluorescence resonance energy transfer (FRET) screening assays yielded a steroid derivative (NSC59276) and an ellipticine analog (NSC338258) from the NCI diversity library of small molecules. Compound NSC59276 targets the BCL2 i-motif and subsequently decreases mRNA and protein levels that leads to increased sensitivity in etoposide-resistant Burkitt’s and mantle cell lymphoma cell lines in vitro and in vivo (Kendrick et al., Nature Chemistry, under revision 2013). Similarly for the MYC G-quadruplex, NSC338258 down-regulates MYC expression and induces cytotoxicity in Burkitt’s lymphoma cell lines (Brown et al., J Biol Chem. 2011). Here, we assess the efficacy of the NSC59276 and NSC338258 as proof of principle for the targeting of BCL2/MYC concurrently in DLBCL, which has clinical implications for improving treatment for the most aggressive DLBCL. Methods We evaluated the cytotoxic and chemosensitizing effects of the BCL2 and MYC inhibitors using the MTS cytotoxcity assay in a DLBCL cell line model that consists of varied BCL2/MYC expression levels and mechanisms of regulation (Table 1). The cytotoxicity assays were conducted with either NSC59276 (BCL2i) or NSC338258 (MYCi) alone or concurrently in combination with standard chemotherapy agents for DLBCL (cyclophosamide and doxorubicin). Results The simultaneous targeting of BCL2/MYC with BCL2i and MYCi in combination with cyclophosphamide treatment had a potent effect on decreasing cell viability by 23–64% compared to cyclophosphamide alone. This effect was observed in DLBCL cell lines that over-express BCL2/MYC regardless of mechanism of deregulation and was negligible in the HT cells that do not express detectable levels. Interestingly, the most significant decrease in cell viability was seen in cell lines with BCL2/MYC gene amplification. Furthermore, BCL2i and MYCi had a synergistic effect on lowering cyclophosphamide IC50 concentration by 30- to a 100-fold in cell lines, particularly of the ABC subtype. Cell viability and cyclosphosphamide IC50 were also decreased when cells were treated with BCL2i or MYCi; however, BCL2i alone had a more significant effect than MYCi. A similar, but less pronounced effect was observed with doxorubicin combination experiments. Conclusion These data support our hypothesis that modulation of BCL2 and MYC with transcriptional repressors in combination with standard chemotherapy agents will improve the efficacy of chemotherapy alone. Further investigations that are ongoing will determine if the combination treated DLBCL cells are more significantly undergoing apoptosis compared to cyclophosphamide or doxorubicin alone. This is a novel, alternative approach of using small molecules that target BCL2 and MYC DNA secondary structures to down-regulate expression and act as chemosensitizing agents to improve current chemotherapy in refractory patients. Disclosures: Hurley: TetraGene: Consultancy, Equity Ownership.

scholarly journals DNA secondary structures: stability and function of G-quadruplex structures

2012 ◽  
Vol 13 (11) ◽  
pp. 770-780 ◽  
Author(s):  
Matthew L. Bochman ◽  
Katrin Paeschke ◽  
Virginia A. Zakian
Keyword(s):  
Secondary Structures ◽  
G Quadruplex ◽  
Dna Secondary Structures ◽  
And Function

Hybrid Imidazole-Pyridine Derivatives: An Approach to Novel Anticancer DNA Intercalators

2020 ◽  
Vol 27 (1) ◽  
pp. 154-169 ◽  
Author(s):  
Claudiu N. Lungu ◽  
Bogdan Ionel Bratanovici ◽  
Maria Mirabela Grigore ◽  
Vasilichia Antoci ◽  
Ionel I. Mangalagiu
Keyword(s):  
Experimental Data ◽  
Antimicrobial Properties ◽  
Qsar Model ◽  
Therapeutic Effectiveness ◽  
Computational Results ◽  
Pyridine Derivatives ◽  
Quadruplex Dna ◽  
Dna Intercalators ◽  
Structure Activity ◽  
G Quadruplex

Lack of specificity and subsequent therapeutic effectiveness of antimicrobial and antitumoral drugs is a common difficulty in therapy. The aim of this study is to investigate, both by experimental and computational methods, the antitumoral and antimicrobial properties of a series of synthesized imidazole-pyridine derivatives. Interaction with three targets was discussed: Dickerson-Drew dodecamer (PDB id 2ADU), G-quadruplex DNA string (PDB id 2F8U) and DNA strain in complex with dioxygenase (PDB id 3S5A). Docking energies were computed and represented graphically. On them, a QSAR model was developed in order to further investigate the structure-activity relationship. Results showed that synthesized compounds have antitumoral and antimicrobial properties. Computational results agreed with the experimental data.

Emerging Role of G-quadruplex DNA as Target in Anticancer Therapy

2017 ◽  
Vol 22 (44) ◽  
pp. 6612-6624 ◽  
Author(s):  
Graziella Cimino-Reale ◽  
Nadia Zaffaroni ◽  
Marco Folini
Keyword(s):  
Anticancer Therapy ◽  
Quadruplex Dna ◽  
G Quadruplex
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