Modeling of mechanochemical DNA cleavage by the action of ultrasound

Nechipurenko, Dmitry; Il’icheva, I. A.; Khodikov, Mingian V.; Poptsova, Maria; Nechipurenko, Yu. D.; Grokhovsky, S. L.

doi:10.1134/s000635091406013x

Cited by 7 publications

(7 citation statements)

References 17 publications

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“…Segmentation of DNA by sonication or other methods used in NGS provide tremendous amount of data concerning such an unusual mechanical property of DNA as the susceptibility to cleavage. Our approach opens up new possibilities for studies of both DNA physics and its relationships with double helix structure and epigenetics 15 .…”

Section: Discussionmentioning

confidence: 99%

“…The BAM files with WGS read alignments on a reference genome were downloaded from the FTP server of the 1000 Genomes project (ftp://ftp.1000genomes.ebi.ac.uk/vol1/ftp/phase3/data/). SAMtools suit was used to filter reads that only map on a forward strand of all autosomes of the human genome (excluding X and Y chromosomes) (samtools view -f 35 -F 4 input.bam {1..22}> filtered.bam) 15 . We also tested whether our filtration criteria affect average cleavage rates: we tested several other scenarios of filtration on 5 random datasets of the 1000 Genomes project.…”

Section: Methodsmentioning

confidence: 99%

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A Method for Identification of the Methylation Level of CpG Islands From NGS Data

Урошлев

Abdullaev

Umarova

et al. 2020

Sci Rep

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In the course of sample preparation for Next Generation Sequencing (NGS), DNA is fragmented by various methods. Fragmentation shows a persistent bias with regard to the cleavage rates of various dinucleotides. With the exception of CpG dinucleotides the previously described biases were consistent with results of the DNA cleavage in solution. Here we computed cleavage rates of all dinucleotides including the methylated CpG and unmethylated CpG dinucleotides using data of the Whole Genome Sequencing datasets of the 1000 Genomes project. We found that the cleavage rate of CpG is significantly higher for the methylated CpG dinucleotides. Using this information, we developed a classifier for distinguishing cancer and healthy tissues based on their CpG islands statuses of the fragmentation. A simple Support Vector Machine classifier based on this algorithm shows an accuracy of 84%. The proposed method allows the detection of epigenetic markers purely based on mechanochemical DNA fragmentation, which can be detected by a simple analysis of the NGS sequencing data.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

A Method for Identification of the Methylation Level of CpG Islands From NGS Data

Урошлев

Abdullaev

Umarova

et al. 2020

Sci Rep

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“…In the works of Grokhovsky and co-authors, the non-random character of the ultrasound-induced fragmentation of DNA was shown: the frequency of the DNA sugar-phosphate backbone breaks strongly depends on the base sequence. [1][2][3][4] With increased employment of mechanochemical DNA cleavage (ultrasound-induced cleavage in particular) as part of nextgeneration sequencing (NGS), much data confirming these findings has accumulated. [5,6] Grokhovsky and co-authors carried out experiments on plasmid DNA, and the NGS results were analyzed in relation to eukaryotic DNA.…”

Section: Introduction: Mechanochemical Cleavage Of Dnamentioning

confidence: 99%

“…It was proposed in ref. [4] that the increase in the frequency of DNA cleavage is related to an increase of the projection on the DNA axis of the bond undergoing cleavage. The increase of the bond projection ensures an increase of the force applied to this bond upon stretching of the sugar‐phosphate backbone in the process of the DNA stretching upon the cavitation bubble collapse.…”

Section: Introduction: Mechanochemical Cleavage Of Dnamentioning

confidence: 99%

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A New Bias Site for Epigenetic Modifications: How Non‐Canonical GC Base Pairs Favor Mechanochemical Cleavage of DNA

2020

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Properties of non-canonical GC base pairs and their relations with mechanochemical cleavage of DNA are analyzed. A hypothesis of the involvement of the transient GC wobble base pairs both in the mechanisms of the mechanochemical cleavage of DNA and epigenetic mechanisms involving of 5-methylcytosine, is proposed. The hypothesis explains the increase in the frequency of the breaks of the sugar-phosphate backbone of DNA after cytosines, the asymmetric character of these breaks, and an increase in break frequency in CpG after cytosine methylation. As an alternative hypothesis, probable implication of GC + Hoogsteen base pairs is considered, which now exemplify the best-studied non-canonical GC base pairs in the DNA double helix. Also see the video abstract here https://youtu.be/EUunVWL0ptw. 2. The Volatile Nature of Cytosine: Tautomerism and Protonation The cause of the cleavage frequency increase can be traced to the properties of cytosine. An increased ability to create a tautomer (imino) form is an inherent feature of cytosine, and this is observed in the 1 H 15 N NMR

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Reversible and Irreversible Mechanical Damaging of Large Double-Stranded DNA upon Electrospraying

2016

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Electrohydrodynamic spraying (or electrospaying, ES) of DNA solutions is an attractive technique for applications in mass spectrometry, in microarray fabrication, and in generation of DNA nanoaerosols. Here we report how ES affects DNA structure and evaluate possible ways to reduce DNA damage upon ES. It is shown that under any ES conditions, linear λ-phage DNA is subjected to intensive rupture producing a mixture of fragments. In addition to such fragmentation, notable reversible changes in the DNA structure were revealed by a slight increase in DNA electrophoretic mobility. The degree of fragmentation was shown to decrease with decreased DNA length and with increased flow rate through the ES capillary. Fragments shorter than 5 kbp did not show any notable damage upon ES. Both experimental data and theoretical estimations of the forces acting on DNA during ES indicate that DNA is damaged by mechanical forces, and the damage takes place in the vicinity of the Taylor cone tip, presumably due to the high shear stress or/and viscous drag forces operating there. Condensation of λ-DNA with hexamminecobalt(III) ions completely protected it from any damage upon ES.

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Modeling of mechanochemical DNA cleavage by the action of ultrasound

Cited by 7 publications

References 17 publications

A Method for Identification of the Methylation Level of CpG Islands From NGS Data

A Method for Identification of the Methylation Level of CpG Islands From NGS Data

A New Bias Site for Epigenetic Modifications: How Non‐Canonical GC Base Pairs Favor Mechanochemical Cleavage of DNA

Reversible and Irreversible Mechanical Damaging of Large Double-Stranded DNA upon Electrospraying

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