Nejvíce citovaný článek - PubMed ID 31967649
Structures and stability of simple DNA repeats from bacteria
G-quadruplexes (G4) are stabilized by intra-quartet hydrogen bonds stacking between quartets, as well as specific and non-specific ionic interactions. Cation effects on G-quadruplexes differ significantly from those on duplexes, and specific cation coordination is indeed required to stabilize G4 structures. Most studies so far involve "standard" concentrations of potassium or sodium cations because of their prevalence in human cells, but several other monovalent and divalent cations may promote quadruplex formation. In addition, ionic strength may be different in other organisms such as Halophiles: the intracellular cation (potassium) concentration in salt-loving organisms such as Haloferax volcanii can be extremely high. In this study, we first performed a bioinformatics analysis of G4 propensity in halophiles and analyzed the impact of altering ionic strength or ionic balance on G4 or hairpin duplex stability. We then present a detailed and quantitative assessment of salt effect on a variety of duplex and quadruplex sequences. Over a dozen different quadruplex and duplex sequences were investigated by FRET melting and UV melting experiments. In addition, changes in sodium/potassium balance possibly occurring in human cells have a modest effect on G4-duplex competition. We also confirm that lithium is rather a "G4-indifferent" than a G4-destabilizing cation.
- Klíčová slova
- Cations, Duplex-quadruplex competition, G-quadruplex, Halophile, Ionic strength,
- Publikační typ
- časopisecké články MeSH
Noncanonical secondary structures in nucleic acids have been studied intensively in recent years. Important biological roles of cruciform structures formed by inverted repeats (IRs) have been demonstrated in diverse organisms, including humans. Using Palindrome analyser, we analyzed IRs in all accessible bacterial genome sequences to determine their frequencies, lengths, and localizations. IR sequences were identified in all species, but their frequencies differed significantly across various evolutionary groups. We detected 242,373,717 IRs in all 1,565 bacterial genomes. The highest mean IR frequency was detected in the Tenericutes (61.89 IRs/kbp) and the lowest mean frequency was found in the Alphaproteobacteria (27.08 IRs/kbp). IRs were abundant near genes and around regulatory, tRNA, transfer-messenger RNA (tmRNA), and rRNA regions, pointing to the importance of IRs in such basic cellular processes as genome maintenance, DNA replication, and transcription. Moreover, we found that organisms with high IR frequencies were more likely to be endosymbiotic, antibiotic producing, or pathogenic. On the other hand, those with low IR frequencies were far more likely to be thermophilic. This first comprehensive analysis of IRs in all available bacterial genomes demonstrates their genomic ubiquity, nonrandom distribution, and enrichment in genomic regulatory regions. IMPORTANCE Our manuscript reports for the first time a complete analysis of inverted repeats in all fully sequenced bacterial genomes. Thanks to the availability of unique computational resources, we were able to statistically evaluate the presence and localization of these important regulatory sequences in bacterial genomes. This work revealed a strong abundance of these sequences in regulatory regions and provides researchers with a valuable tool for their manipulation.
- Klíčová slova
- Palindrome analyser, bacteria domain, bacterial genome analysis, inverted repeats,
- MeSH
- Bacteria genetika MeSH
- fylogeneze MeSH
- genomika * MeSH
- lidé MeSH
- replikace DNA * MeSH
- sekvence nukleotidů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Interactions between nucleic acids and proteins are some of the most important interactions in biology because they are the cornerstones for fundamental biological processes, such as replication, transcription, and recombination [...].
- Klíčová slova
- DNA base sequence, DNA structure, G-quadruplex, Z-DNA, cruciform, nucleic acid–protein interactions,
- MeSH
- DNA chemie MeSH
- G-kvadruplexy * MeSH
- konformace nukleové kyseliny MeSH
- molekulární struktura MeSH
- nukleové kyseliny * MeSH
- proteiny metabolismus MeSH
- Publikační typ
- úvodníky MeSH
- Názvy látek
- DNA MeSH
- nukleové kyseliny * MeSH
- proteiny MeSH
Cruciforms occur when inverted repeat sequences in double-stranded DNA adopt intra-strand hairpins on opposing strands. Biophysical and molecular studies of these structures confirm their characterization as four-way junctions and have demonstrated that several factors influence their stability, including overall chromatin structure and DNA supercoiling. Here, we review our understanding of processes that influence the formation and stability of cruciforms in genomes, covering the range of sequences shown to have biological significance. It is challenging to accurately sequence repetitive DNA sequences, but recent advances in sequencing methods have deepened understanding about the amounts of inverted repeats in genomes from all forms of life. We highlight that, in the majority of genomes, inverted repeats are present in higher numbers than is expected from a random occurrence. It is, therefore, becoming clear that inverted repeats play important roles in regulating many aspects of DNA metabolism, including replication, gene expression, and recombination. Cruciforms are targets for many architectural and regulatory proteins, including topoisomerases, p53, Rif1, and others. Notably, some of these proteins can induce the formation of cruciform structures when they bind to DNA. Inverted repeat sequences also influence the evolution of genomes, and growing evidence highlights their significance in several human diseases, suggesting that the inverted repeat sequences and/or DNA cruciforms could be useful therapeutic targets in some cases.
- Klíčová slova
- DNA base sequence, DNA structure, DNA supercoiling, cruciform, epigenetics, genome stability, inverted repeat, replication, transcription,
- MeSH
- DNA genetika MeSH
- konformace nukleové kyseliny MeSH
- křížová struktura DNA MeSH
- lidé MeSH
- nukleové kyseliny * MeSH
- obrácené repetice MeSH
- repetitivní sekvence nukleových kyselin genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- DNA MeSH
- křížová struktura DNA MeSH
- nukleové kyseliny * MeSH
Parasitic helminths infecting humans are highly prevalent infecting ∼2 billion people worldwide, causing inflammatory responses, malnutrition and anemia that are the primary cause of morbidity. In addition, helminth infections of cattle have a significant economic impact on livestock production, milk yield and fertility. The etiological agents of helminth infections are mainly Nematodes (roundworms) and Platyhelminths (flatworms). G-quadruplexes (G4) are unusual nucleic acid structures formed by G-rich sequences that can be recognized by specific G4 ligands. Here we used the G4Hunter Web Tool to identify and compare potential G4 sequences (PQS) in the nuclear and mitochondrial genomes of various helminths to identify G4 ligand targets. PQS are nonrandomly distributed in these genomes and often located in the proximity of genes. Unexpectedly, a Nematode, Ascaris lumbricoides, was found to be highly enriched in stable PQS. This species can tolerate high-stability G4 structures, which are not counter selected at all, in stark contrast to most other species. We experimentally confirmed G4 formation for sequences found in four different parasitic helminths. Small molecules able to selectively recognize G4 were found to bind to Schistosoma mansoni G4 motifs. Two of these ligands demonstrated potent activity both against larval and adult stages of this parasite.
- MeSH
- cizopasní červi genetika MeSH
- G-kvadruplexy * MeSH
- genom MeSH
- hlístice * genetika MeSH
- lidé MeSH
- ligandy MeSH
- paraziti genetika MeSH
- ploštěnci * genetika MeSH
- skot MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ligandy MeSH
The importance of gene expression regulation in viruses based upon G-quadruplex may point to its potential utilization in therapeutic targeting. Here, we present analyses as to the occurrence of putative G-quadruplex-forming sequences (PQS) in all reference viral dsDNA genomes and evaluate their dependence on PQS occurrence in host organisms using the G4Hunter tool. PQS frequencies differ across host taxa without regard to GC content. The overlay of PQS with annotated regions reveals the localization of PQS in specific regions. While abundance in some, such as repeat regions, is shared by all groups, others are unique. There is abundance within introns of Eukaryota-infecting viruses, but depletion of PQS in introns of bacteria-infecting viruses. We reveal a significant positive correlation between PQS frequencies in dsDNA viruses and corresponding hosts from archaea, bacteria, and eukaryotes. A strong relationship between PQS in a virus and its host indicates their close coevolution and evolutionarily reciprocal mimicking of genome organization.
- Klíčová slova
- G-quadruplex, G4Hunter, bioinformatics, coevolution, dsDNA, host, virus,
- MeSH
- Archaea virologie MeSH
- Bacteria virologie MeSH
- DNA genetika MeSH
- G-kvadruplexy * MeSH
- genom virový * MeSH
- genom MeSH
- lidé MeSH
- regulace genové exprese MeSH
- virové proteiny genetika MeSH
- viry genetika MeSH
- výpočetní biologie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- DNA MeSH
- virové proteiny MeSH
Nucleic acid-binding proteins are traditionally divided into two categories: With the ability to bind DNA or RNA. In the light of new knowledge, such categorizing should be overcome because a large proportion of proteins can bind both DNA and RNA. Another even more important features of nucleic acid-binding proteins are so-called sequence or structure specificities. Proteins able to bind nucleic acids in a sequence-specific manner usually contain one or more of the well-defined structural motifs (zinc-fingers, leucine zipper, helix-turn-helix, or helix-loop-helix). In contrast, many proteins do not recognize nucleic acid sequence but rather local DNA or RNA structures (G-quadruplexes, i-motifs, triplexes, cruciforms, left-handed DNA/RNA form, and others). Finally, there are also proteins recognizing both sequence and local structural properties of nucleic acids (e.g., famous tumor suppressor p53). In this mini-review, we aim to summarize current knowledge about the amino acid composition of various types of nucleic acid-binding proteins with a special focus on significant enrichment and/or depletion in each category.
- Klíčová slova
- DNA, G-quadruplex, RNA, Z-DNA, Z-RNA, amino acid composition, cruciform, i-motif, protein binding, triplex,
- MeSH
- DNA vazebné proteiny genetika MeSH
- DNA genetika ultrastruktura MeSH
- G-kvadruplexy MeSH
- konformace nukleové kyseliny * MeSH
- leucinové zipy genetika MeSH
- lidé MeSH
- nukleoproteiny genetika ultrastruktura MeSH
- RNA chemie ultrastruktura MeSH
- sekvence aminokyselin genetika MeSH
- transportní proteiny genetika ultrastruktura MeSH
- Z-DNA MeSH
- zinkové prsty genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- DNA vazebné proteiny MeSH
- DNA MeSH
- nukleoproteiny MeSH
- RNA MeSH
- transportní proteiny MeSH
- Z-DNA MeSH