Dimeric G-quadruplex motifs-induced NFRs determine strong replication origins in vertebrates

Poulet-Benedetti, Jérémy; Tonnerre-Doncarli, Caroline; Valton, Anne‐Laure; Laurent, Marc; Gérard, Marie; Barinova, Natalja; Parisis, Nikolaos; Massip, Florian; Picard, Franck; Prioleau, Marie‐Noëlle

doi:10.1101/2022.08.17.504255

Cited by 2 publications

(3 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, two G4-containing ORIs can drive DNA replication initiation in the chicken DT40 cell line (Valton et al, 2014, Prorok et al, 2019). More recently, Poulet-Benedetti et al (2023) found that two G4-forming motifs on the same strand are sufficient for replication initiation. According to this study, however, tandem G4s associated with ORIs tend to be located in NDR next to well-positioned nucleosomes, which is different from the GGN clusters studied here that are strongly associated with nucleosomes.…”

Section: Discussionmentioning

confidence: 99%

“…Several articles reported an association between ORIs and atypical DNA secondary structures formed by stacked arrangements of planar G-tetrads stabilized by Hoogsteen hydrogen bonding, called G-quadruplexes (G4) (Hansen et al, 2010; Cayrou et al, 2011; Besnard et al, 2012; Gindin et al, 2014; Valton et al, 2014; Smith et al, 2016; Prorok et al, 2019). While the role of G4s in ORI activity is still a matter of debate (Valton and Prioleau 2016; Akerman et al, 2020), a recent pre-print demonstrated that engineering dimeric G4 motifs in the same DNA strand is sufficient to induce the formation of a minimal ORI (Poulet-Benedetti et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The topography of DNA replication origins in Eukarya: GGN clusters, landmark nucleosomes, CDC6 and G4 structures

Bastolla,

Gómez-Pinto,

Vergara

et al. 2024

Preprint

View full text Add to dashboard Cite

Background: We recently identified tandem repeats of GGN triplets as a sequence motif strongly enriched in the DNA replication origins (ORIs) of the Arabidopsis thaliana genome, where it correlates with the ORI strength quantified through short nascent strands sequencing. Results: Here we show that clusters of four or more GGN repeats separated by short tracts (<7 nucleotides) are present in more than 65% ORIs of six model eukaryotic organisms: Leishmania major, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus and Homo sapiens. The measured percentages vary with the experimental technique adopted for ORI determination. For all studied techniques and organisms, ORIs are significantly prone to be located within or near strong GGN clusters, although these are neither necessary nor sufficient for ORI activation. Interestingly, for same experimental technique, the association between ORIs and GGN clusters was stronger al later developmental stages for all organisms for which we could perform this comparison. In accordance with a biophysical model of nucleosome positioning, the GGN clusters strongly favor nucleosome occupancy. At the same time, both GGN clusters and ORIs occur frequently within 1kb from nucleosome-depleted regions (NDR). We propose a structural model based on chromatin secondary structure in which the NDR and the well-positioned nucleosome at the GGN are close in space, which may favor functional interactions. We hypothesize that the presence of GGN at ORIs arose in part for promoting the above nucleosome organization Moreover, at least in Arabidopsis, the replication protein CDC6 is very strongly associated with GGN clusters. NMR experiments showed that clusters of at least four GGN can form G-quadruplex (G4) in vitro. Our data support the view that GGN clusters are formed through the interplay of mutational processes (GC skew at ORIs plus triplet expansion), and that similar mutational processes, i.e. AT skew at transcription start sites (TSS) and ORIs, might facilitate the formation of the NDR, thus favoring the evolvability of chromatin. Conclusions: GGN clusters are easily evolvable sequence motifs enriched at ORIs of eukaryotic genomes. They favor G4 secondary structure and a nucleosome organization that may unify the apparent discrepancy between ORIs of higher eukaryotes and yeast.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The topography of DNA replication origins in Eukarya: GGN clusters, landmark nucleosomes, CDC6 and G4 structures

Bastolla,

Gómez-Pinto,

Vergara

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…G4s have been implicated in a wide range of biological processes, including transcription (ref? ), telomere maintenance ( 24 ), DNA replication ( 25, 26 ) and repair ( 27, 28 ), and RNA processing and translation ( 29, 30 ). As regulatory elements, G4s act as molecular switches, modulating gene expression or protein-DNA associations ( 31, 32 ).…”

Section: Introductionmentioning

confidence: 99%

G-quadruplexes inHaloferax volcanii

Aktary,

Cucchiarini,

Vesco

et al. 2024

Preprint

View full text Add to dashboard Cite

The archaeal domain is a taxonomically rich component of microbial communities that inhabit a wide range of habitats on Earth, including the human body. Phylogenomic analyses have indicated that archaea represent the closest known relatives of eukaryotes, thus suggesting that eukaryotes may have evolved from an archaeal ancestor. G-quadruplex structures (G4), formed by guanine rich sequences, are among the most intensively studied local DNA/RNA structures and regulate key biological processes such as replication and gene expression. A bioinformatics analysis of the genome of the salt-loving archaea H. volcanii revealed a large number of potential G4 sequences (PQS). Biophysical analyses showed that a representative panel of these sequences form stable G4 structures under physiological conditions in vitro. In addition, immunofluorescence experiments using the G4-specific antibody, BG4, detected G4s in vivo at the single-cell level with super-resolution microscopy. Moreover, we directly visualized G4 in exponentially growing or stationary cells both at the DNA and RNA levels. G4s were also observed in the RNA and DNA of the hyperthermophile archaeon T. barophilus. Finally, we identified helicases potentially involved in G4 unfolding. Together, with H. volcanii as a new model, our work helps to fill the gap between bacteria and eukaryotic organisms for G4 studies and will aid in uncovering the evolutionary history of G4 structures in the tree of life.

show abstract

Dimeric G-quadruplex motifs-induced NFRs determine strong replication origins in vertebrates

Cited by 2 publications

References 43 publications

The topography of DNA replication origins in Eukarya: GGN clusters, landmark nucleosomes, CDC6 and G4 structures

The topography of DNA replication origins in Eukarya: GGN clusters, landmark nucleosomes, CDC6 and G4 structures

G-quadruplexes inHaloferax volcanii

Contact Info

Product

Resources

About