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 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.

Human Pif1 helicase is a G-quadruplex DNA-binding protein with G-quadruplex DNA-unwinding activity

2010 ◽  
Vol 430 (1) ◽  
pp. 119-128 ◽  
Author(s):  
Cyril M. Sanders
Keyword(s):  
Dna Binding ◽  
Dna Sequences ◽  
Genome Stability ◽  
Dna Helicase ◽  
Dna Unwinding ◽  
Helicase Domain ◽  
Quadruplex Dna ◽  
G4 Dna ◽  
G Quadruplex ◽  
Pif1 Helicase

Pif1 proteins are helicases that in yeast are implicated in the maintenance of genome stability. One activity of Saccharomyces cerevisiae Pif1 is to stabilize DNA sequences that could otherwise form deleterious G4 (G-quadruplex) structures by acting as a G4 resolvase. The present study shows that human Pif1 (hPif1, nuclear form) is a G4 DNA-binding and resolvase protein and that these activities are properties of the conserved helicase domain (amino acids 206–620 of 641, hPifHD). hPif1 preferentially bound synthetic G4 DNA relative to ssDNA (single-stranded DNA), dsDNA (double-stranded DNA) and a partially single-stranded duplex DNA helicase substrate. G4 DNA unwinding, but not binding, required an extended (>10 nucleotide) 5′ ssDNA tail, and in competition assays, G4 DNA was an ineffective suppressor of helicase activity compared with ssDNA. These results suggest a distinction between the determinants of G4 DNA binding and the ssDNA interactions required for helicase action and that hPif1 may act on G4 substrates by binding alone or as a resolvase. Human Pif1 could therefore have a role in processing G4 structures that arise in the single-stranded nucleic acid intermediates formed during DNA replication and gene expression.

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 ATRX promotes heterochromatin formation to protect cells from G-quadruplex DNA-mediated stress

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yu-Ching Teng ◽  
Aishwarya Sundaresan ◽  
Ryan O’Hara ◽  
Vincent U. Gant ◽  
Minhua Li ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Genome Stability ◽  
Helicase Domain ◽  
Quadruplex Dna ◽  
Heterochromatin Formation ◽  
Replicative Stress ◽  
G4 Dna ◽  
Mutation Burden ◽  
G Quadruplex ◽  
Dna Replication Stress

AbstractATRX is a tumor suppressor that has been associated with protection from DNA replication stress, purportedly through resolution of difficult-to-replicate G-quadruplex (G4) DNA structures. While several studies demonstrate that loss of ATRX sensitizes cells to chemical stabilizers of G4 structures, the molecular function of ATRX at G4 regions during replication remains unknown. Here, we demonstrate that ATRX associates with a number of the MCM replication complex subunits and that loss of ATRX leads to G4 structure accumulation at newly synthesized DNA. We show that both the helicase domain of ATRX and its H3.3 chaperone function are required to protect cells from G4-induced replicative stress. Furthermore, these activities are upstream of heterochromatin formation mediated by the histone methyltransferase, ESET, which is the critical molecular event that protects cells from G4-mediated stress. In support, tumors carrying mutations in either ATRX or ESET show increased mutation burden at G4-enriched DNA sequences. Overall, our study provides new insights into mechanisms by which ATRX promotes genome stability with important implications for understanding impacts of its loss on human disease.

scholarly journals EXO1 resection at G-quadruplex structures facilitates resolution and replication

2020 ◽  
Vol 48 (9) ◽  
pp. 4960-4975 ◽  
Author(s):  
Susanna Stroik ◽  
Kevin Kurtz ◽  
Kevin Lin ◽  
Sergey Karachenets ◽  
Chad L Myers ◽  
...  
Keyword(s):  
Dna Replication ◽  
Genomic Instability ◽  
Secondary Structures ◽  
Replication Forks ◽  
End Joining ◽  
G Quadruplex ◽  
Exonuclease 1 ◽  
Telomere Loss

Abstract G-quadruplexes represent unique roadblocks to DNA replication, which tends to stall at these secondary structures. Although G-quadruplexes can be found throughout the genome, telomeres, due to their G-richness, are particularly predisposed to forming these structures and thus represent difficult-to-replicate regions. Here, we demonstrate that exonuclease 1 (EXO1) plays a key role in the resolution of, and replication through, telomeric G-quadruplexes. When replication forks encounter G-quadruplexes, EXO1 resects the nascent DNA proximal to these structures to facilitate fork progression and faithful replication. In the absence of EXO1, forks accumulate at stabilized G-quadruplexes and ultimately collapse. These collapsed forks are preferentially repaired via error-prone end joining as depletion of EXO1 diverts repair away from error-free homology-dependent repair. Such aberrant repair leads to increased genomic instability, which is exacerbated at chromosome termini in the form of dysfunction and telomere loss.

scholarly journals G-rich telomeric and ribosomal DNA sequences from the fission yeast genome form stable G-quadruplex DNA structuresin vitroand are unwound by the Pfh1 DNA helicase

2016 ◽  
Vol 44 (13) ◽  
pp. 6213-6231 ◽  
Author(s):  
Marcus Wallgren ◽  
Jani B. Mohammad ◽  
Kok-Phen Yan ◽  
Parham Pourbozorgi-Langroudi ◽  
Mahsa Ebrahimi ◽  
...  
Keyword(s):  
Fission Yeast ◽  
Ribosomal Dna ◽  
Dna Sequences ◽  
Dna Helicase ◽  
Yeast Genome ◽  
Quadruplex Dna ◽  
G Quadruplex

scholarly journals Evidences for Piperine inhibiting cancer by targeting human G-quadruplex DNA sequences

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Arpita Tawani ◽  
Ayeman Amanullah ◽  
Amit Mishra ◽  
Amit Kumar
Keyword(s):  
Dna Sequences ◽  
Quadruplex Dna ◽  
G Quadruplex
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