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1.
Biochem Biophys Res Commun ; 692: 149349, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38056160

RESUMO

While it is well established that a mere 2% of human DNA nucleotides are involved in protein coding, the remainder of the DNA plays a vital role in the preservation of normal cellular genetic function. A significant proportion of tandem repeats (TRs) are present in non-coding DNA. TRs - specific sequences of nucleotides that entail numerous repetitions of a given fragment. In this study, we employed our novel algorithm grounded in finite automata theory, which we refer to as Dafna, to investigate for the first time the likelihood of these nucleotide sequences forming non-canonical DNA structures (NS). Such structures include G-quadruplexes, i-motifs, hairpins, and triplexes. The tandem repeats under consideration in our research encompassed sequences containing 1 to 6 nucleotides per repeated fragment. For comparison, we employed a set of randomly generated sequences of the same length (60 nucleotides) as a benchmark. The outcomes of our research exposed a disparity between the potential for NS formation in random sequences and tandem repeats. Our findings affirm that the propensity of DNA and RNA to form NS is closely tied to various genetic disorders, including Huntington's disease, Fragile X syndrome, and Friedreich's ataxia. In the concluding discussion, we present a proposal for a new therapeutic mechanism to address these diseases. This novel approach revolves around the ability of specific nucleic acid fragments to form multiple types of NS.


Assuntos
Relevância Clínica , Sequências de Repetição em Tandem , Humanos , Sequências de Repetição em Tandem/genética , DNA/química , Sequência de Bases , Nucleotídeos
2.
Gene ; 820: 146277, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35149154

RESUMO

In the present review, numerous experimental and theoretical data describing the properties of non-canonical DNA structures (NSs) are analyzed. NSs (G-quadruplex, i-motif, hairpin, and triplex) play an important role in epigenetic processes (including the genetic variability of viruses), are prone to energetically low-cost conformational transformations and can very effectively be used in the design of nanoscale devices. Numerous experimental data have been analyzed in connection with the so-called oligonucleotides-transformers (nucleotide sequences that able to fold not only into one, but also into several NSs). These sequences were recently predicted by our calculations using automata and graph theories ("Dafna" algorithm). Possible applications of the oligonucleotides-transformers in nanoengineering and genetic editing of organisms are considered.


Assuntos
DNA/química , Biologia Molecular , Nanotecnologia , Conformação de Ácido Nucleico , Oligonucleotídeos , Animais , Sequência de Bases , Quadruplex G , Engenharia Genética , Humanos
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