Structure and Function of Multimeric G-Quadruplexes

Kolesnikova, Sofia; Curtis, Edward A.

doi:10.3390/molecules24173074

Cited by 80 publications

(68 citation statements)

References 134 publications

(201 reference statements)

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“…The activation of the MCM helicase occurs at the G1-S transition, but only 20-30% of the pre-RCs are activated in S phase. A fundamental characteristic of G4 is its ability to form several structures 47 , including folded and unfolded forms. These two forms might regulate the OFF stage (pre-RC) or the ON stage (initiation) of a replication origin; Exogenous G4 sequences able to form G4 structures do not inhibit the formation of pre-RCs in Xenopus egg extracts, but do compete with the firing of replication origins 48 .…”

Section: Discussionmentioning

confidence: 99%

A predictable conserved DNA base composition signature defines human core DNA replication origins

et al. 2020

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DNA replication initiates from multiple genomic locations called replication origins. In metazoa, DNA sequence elements involved in origin specification remain elusive. Here, we examine pluripotent, primary, differentiating, and immortalized human cells, and demonstrate that a class of origins, termed core origins, is shared by different cell types and host ~80% of all DNA replication initiation events in any cell population. We detect a shared G-rich DNA sequence signature that coincides with most core origins in both human and mouse genomes. Transcription and G-rich elements can independently associate with replication origin activity. Computational algorithms show that core origins can be predicted, based solely on DNA sequence patterns but not on consensus motifs. Our results demonstrate that, despite an attributed stochasticity, core origins are chosen from a limited pool of genomic regions. Immortalization through oncogenic gene expression, but not normal cellular differentiation, results in increased stochastic firing from heterochromatin and decreased origin density at TAD borders.

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Section: Discussionmentioning

confidence: 99%

A predictable conserved DNA base composition signature defines human core DNA replication origins

et al. 2020

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“…G-quadruplexes are secondary nucleic acid structures formed in guanine-rich strands (Burge et al, 2006 ; Vorlíčková et al, 2012 ; Kolesnikova and Curtis, 2019 ). These have been detected in various genomes, but most extensively they have been described in human genomes (Chambers et al, 2015 ; Bedrat et al, 2016 ; Hänsel-Hertsch et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

In-Depth Bioinformatic Analyses of Nidovirales Including Human SARS-CoV-2, SARS-CoV, MERS-CoV Viruses Suggest Important Roles of Non-canonical Nucleic Acid Structures in Their Lifecycles

et al. 2020

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Non-canonical nucleic acid structures play important roles in the regulation of molecular processes. Considering the importance of the ongoing coronavirus crisis, we decided to evaluate genomes of all coronaviruses sequenced to date (stated more broadly, the order Nidovirales) to determine if they contain non-canonical nucleic acid structures. We discovered much evidence of putative G-quadruplex sites and even much more of inverted repeats (IRs) loci, which in fact are ubiquitous along the whole genomic sequence and indicate a possible mechanism for genomic RNA packaging. The most notable enrichment of IRs was found inside 5 ′ UTR for IRs of size 12+ nucleotides, and the most notable enrichment of putative quadruplex sites (PQSs) was located before 3 ′ UTR, inside 5 ′ UTR, and before mRNA. This indicates crucial regulatory roles for both IRs and PQSs. Moreover, we found multiple G-quadruplex binding motifs in human proteins having potential for binding of SARS-CoV-2 RNA. Non-canonical nucleic acids structures in Nidovirales and in novel SARS-CoV-2 are therefore promising druggable structures that can be targeted and utilized in the future.

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“…Vertebrate telomeres comprise repeats of the sequence TTAGGG, which in vitro has the interesting property being able to readily interconvert between parallel, antiparallel or mixed hybrid G4 folds depending on experimental conditions, 153 , 154 which in vivo may enable opportunities for regulation based on fold-specific interactions, for example by interacting differentially with particular proteins. There is also emerging evidence for interactions among individual telomeric G4s in vitro that may reflect ways in which G4 impact the overall architecture of telomere chromatin (reviewed in 155 ).…”

Section: Biological Processes Impacted By G-quadruplexesmentioning

confidence: 99%

Fundamentals of G-quadruplex biology

Johnson

2020

Annual Reports in Medicinal Chemistry

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Several decades elapsed between the first descriptions of G-quadruplex nucleic acid structures (G4s) assembled in vitro and the emergence of experimental findings indicating that such structures can form and function in living systems. A large body of evidence now supports roles for G4s in many aspects of nucleic acid biology, spanning processes from transcription and chromatin structure, mRNA processing, protein translation, DNA replication and genome stability, and telomere and mitochondrial function. Nonetheless, it must be acknowledged that some of this evidence is tentative, which is not surprising given the technical challenges associated with demonstrating G4s in biology. Here I provide an overview of evidence for G4 biology, focusing particularly on the many potential pitfalls that can be encountered in its investigation, and briefly discuss some of broader biological processes that may be impacted by G4s including cancer.

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Structure and Function of Multimeric G-Quadruplexes

Cited by 80 publications

References 134 publications

A predictable conserved DNA base composition signature defines human core DNA replication origins

A predictable conserved DNA base composition signature defines human core DNA replication origins

In-Depth Bioinformatic Analyses of Nidovirales Including Human SARS-CoV-2, SARS-CoV, MERS-CoV Viruses Suggest Important Roles of Non-canonical Nucleic Acid Structures in Their Lifecycles

Fundamentals of G-quadruplex biology

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