DNA Base Pairs Research Articles

The Wild-Type tRNA Adenosine Deaminase Enzyme TadA Is Capable of Sequence-Specific DNA Base Editing.

Base editors are genome editing tools that enable site-specific base conversions through the chemical modification of nucleobases in DNA. Adenine base editors (ABEs) convert A ⋅ T to G ⋅ C base pairs in DNA by using an adenosine deaminase enzyme to modify target adenosines to inosine intermediates. Due to the lack of a naturally occurring adenosine deaminase that can modify DNA, ABEs were evolved from a tRNA-deaminating enzyme, TadA. Previous experiments with an ABE comprising a wild-type (wt) TadA showed no detectable activity on DNA, and directed evolution was therefore required to enable this enzyme to accept DNA as a substrate. Here we show that wtTadA can perform base editing in DNA in both bacterial and mammalian cells, with a strict sequence motif requirement of TAC. We leveraged this discovery to optimize a reporter assay to detect base editing levels as low as 0.01 %. Finally, we used this assay along with molecular dynamics simulations of full ABE:DNA complexes to better understand how the sequence recognition of mutant TadA variants change as they accumulate mutations to better edit DNA substrates.

Ordered self-assembly of DNA-modified nanoparticles in salt solutions

DNA-modified nanoparticles (DNA-NPs) have been widely applied in medical diagnosis and biosensors. Molecular dynamics (MD) simulation, a common method to track the dynamic changes of ions, nanoparticles and DNA, is able to predict the assembly behavior of DNA-NP, thus providing a fast and efficient method for precise regulation of experiments. At present, the simulation research of the DNA-NP self-assembly mainly focuses on DNA bonding, while the effects of electrostatic interactions between DNA and DNA, ions and ions, ions and DNA on the self-assembly structure and mechanism have not been systematically studied. We have constructed a coarse-grained model of DNA-NP self-assembly in salt solutions to appropriately simulate the experimental conditions. It can well match the directionality and saturation of DNA base pairing, as well as the electrostatic repulsive interactions between DNA, and ion-related effects. How the distribution of ions, electrostatic shielding and DNA hybridization regulate the assembled structure and kinetic properties of DNA-NP in monovalent or divalent salt solutions with different ionic concentrations are deeply investigated. Our simulated results reveal the thermodynamic stability and reversibility of the ordered self-assembly of DNA-NPs, in accordance with experimental results. They also provide a reasonable explanation for the susceptibility of nanoparticles to aggregation at high salt concentration for multivalent salt environments. Our research gives a preliminary attempt for the simulation of DNA-NP self-assembly in salt solution, provides theoretical guidance for designing DNA nanomaterials with controllable structures and properties, and promotes its research progress in the fields of medical diagnosis and biosensors.

Metal ions recognition and DNA binding properties of four rosin derivatives

Four rosin derivatives containing amide, pyridine and dehydroabietyl sub-units were synthesized. Their selective and sensitive recognition of Cu2+ and Fe3+ ions were confirmed by UV–vis and fluorescence spectra. Their detection limits for Cu2+ and Fe3+ were lower than the maximum allowable levels of Cu2+ and Fe3+ in drinking water. They could displace ethidium bromide (EB) molecules inserted into CT DNA base pairs and induce fluorescence quenching of CT DNA-EB system in a static mode. The negative ΔG values proved that the binding processes of the compounds to CT DNA were spontaneous. The negative values of both ΔH and ΔS solidified that the hydrogen bonds or Van der Waals was the driving force for the interactions between the four compounds and CT DNA. Metal ion recognition and DNA interaction indicate that the number of pyridine rings and the flexibility of the compounds had influence on the strength of the above activities.

Intercalation of anticancer drug Palbociclib with calf-thymus DNA: new insights from molecular spectroscopic, molecular dynamic simulations and cleavage studies

The interaction between the anti-cancer drug Palbociclib (PAL) and calf-thymus DNA (CT-DNA) was investigated using various biophysical techniques in a physiological buffer (pH 7.4). It was found that PAL intercalated into the base pairs of CT-DNA as evidenced from the results of UV-Vis, fluorescence, circular dichroism (CD), competitive binding assay with ethidium bromide (EB) and Hoechst 33258, KI quenching study, the effect of denaturing agent and viscosity measurements. The magnitude of binding constants (106 M−1) at different temperatures suggested strong binding between PAL and CT-DNA during complexation. The observed ΔHo > 0 and ΔSo > 0 indicated that the binding process is primarily driven by hydrophobic interactions. Molecular docking studies indicated partial intercalation of pyridopyrimidine ring between the base pairs of DNA. Free energy surface (FES) analysis derived from metadynamics simulation studies revealed the PAL-induced cleavage of DNA, which was confirmed by gel electrophoresis experiments. Communicated by Ramaswamy H. Sarma

Casting a Wider Net When Fishing for Mechanisms of Anesthesia.

Casting a Wider Net When Fishing for Mechanisms of Anesthesia.

High-Order Quantum-Mechanical Analysis of Hydrogen Bonding in Hachimoji and Natural DNA Base Pairs.

High-order quantum chemistry is applied to hydrogen-bonded natural DNA nucleobase pairs [adenine:thymine (A:T) and guanine:cytosine (G:C)] and non-natural Hachimoji nucleobase pairs [isoguanine:1-methylcytosine (B:S) and 2-aminoimidazo[1,2a][1,3,5]triazin-4(1H)-one:6-amino-5-nitropyridin-2-one (P:Z)] to see how the intermolecular interaction energies and their energetic components (electrostatics, exchange-repulsion, induction/polarization, and London dispersion interactions) vary among the base pairs. We examined the Hoogsteen (HG) geometries in addition to the traditional Watson-Crick (WC) geometries. Coupled-cluster theory through perturbative triples [CCSD(T)] extrapolated to the complete basis set (CBS) limit and high-order symmetry-adapted perturbation theory (SAPT) at the SAPT2+(3)(CCD)δMP2/aug-cc-pVTZ level are used to estimate highly accurate noncovalent interaction energies. Electrostatic interactions are the most attractive component of the interaction energies, but the sum of induction/polarization and London dispersion is nearly as large, for all base pairs and geometries considered. Interestingly, the non-natural Hachimoji base pairs interact more strongly than the corresponding natural base pairs, by -21.8 (B:S) and -0.3 (P:Z) kcal mol-1 in the WC geometries, according to CCSD(T)/CBS. This is consistent with the H-bond distances being generally shorter in the non-natural base pairs. The natural base pairs are energetically more stabilized in their Hoogsteen geometries than in their WC geometries. The Hoogsteen geometry makes the A:T base pair slightly more stable, by -0.8 kcal mol-1, and it greatly stabilizes the G:C+ base pair, by -15.3 kcal mol-1. The G:C+ stabilization is mainly due to the fact that C has typically added a proton when found in Hoogsteen geometries. By contrast, Hoogsteen geometries are substantially less favorable than WC geometries for non-natural Hachimoji base pairs, by 17.3 (B:S) and 13.8 (P:Z) kcal mol-1.

Total evidence phylogenetic analysis of Leiosauridae (Squamata) with focus on the ‘para-anoles’ and description of a new Urostrophus species from the Bolivian Andes

Only since the late 1980s have lizard specialists begun incorporating phylogenetic information to the classification of leiosaurids. These are among the most enigmatic South American lizards, with 35 currently recognised species arranged in six genera. To evaluate their relationships, we assembled a data set based on published and novel information containing 135 morphological characters and 11,235 DNA base pairs (14 loci) for up to 52 terminals, including outgroups. We performed 13 analyses based on different optimality criteria (parsimony, maximum likelihood, and coalescent approach) and indel coding strategies (gaps coded as missing data or as a fifth state). We also evaluated the impact of phenotypic evidence on the phylogeny of leiosaurids, and investigated the level of informativeness and potential sources of topological conflict using a Quartet Sampling analysis. Phylogenetic analyses supported the monophyly of major leiosaurid clades, including subfamilies Enyaliinae and Leiosaurinae, and the ‘para-anoles’ clade (Urostrophus + Anisolepis). However, Urostrophus was inferred as paraphyletic, with U. vautieri forming a clade with Anisolepis. These relationships motivate the synonymization of Anisolepis Boulenger, 1885 with Urostrophus Duméril & Bibron, 1837. The monophyly of Pristidactylus and, surprisingly, of Enyalius, were also challenged, underscoring the need for additional phylogenetic work. Finally, we described Urostrophus chungarae sp. nov. from the Torotoro National Park, Potosí, Bolivia. This apparently rare leiosaurid was inferred as sister to U. gallardoi, a Chacoan species distributed in northern Argentina and southeastern Bolivia. We conclude with a revised classification of Leiosauridae and by pointing out a number of unresolved issues that require further systematic investigation. http://www.zoobank.org/urn:lsid:zoobank.org:pub:F60EB6CB-62B2-4EE3-B1A8-BEE3B2ED7A65

Acetylation of MLH1 by CBP increases cellular DNA mismatch repair activity.

The DNA mismatch repair (MMR) proteins recognize and repair DNA base pair mismatches and insertions/deletions of DNA that have occurred during DNA replication. Additionally, they are involved in regulation of the DNA damage response, including cell cycle checkpoints and apoptosis. Therefore, regulation of these proteins is essential for maintaining genomic integrity. It has been recognized that post-translational modifications, such as phosphorylation, ubiquitination, and acetylation, are being used as an important means to regulate the functions and stability of MMR proteins. Here, we report that a histone acetyltransferase CREB binding protein (CBP) interacts with and acetylates MLH1, a component of the MutLα complex (MLH1-PMS2). Moreover, CBP stabilizes MLH1 by preventing it from degradation via the ubiquitin-proteasome degradation pathway. Consistently, acetylation induced by a pan-histone deacetylase inhibitor, Trichostatin A, promotes the assembly between the MutSα (MSH2-MSH6) and MutLα complexes. Furthermore, overexpression of CBP enhances MMR activities in cells. Overall, our results suggest a novel role of CBP in prolonging MLH1 stability and enhancing MutSα-MutLα complex formation, leading to increased cellular MMR activity.

CVD Graphene Electrode for Direct Electrochemical Detection of Double-Stranded DNA

Understanding and regulating DNA interactions with solvents and redox-active centers opens up new possibilities for improving electrochemical signals and developing adequate biosensors. This work reports the development of a modified indium tin oxide (ITO) electrode by chemical vapor deposition (CVD) of graphene for the detection of double-stranded DNA. The modified electrode shows a better electrical conductivity than ITO, as confirmed by electrochemical impedance spectroscopy (EIS), where a drastic decrease in the charge–transfer resistance, Rct, from ~320 to ~60 Ω was observed. Sequences of double-stranded genomic DNA with a different number of base pairs are evaluated through differential pulse voltammetry (DPV), using ferri/ferrocyanide ([Fe(CN)6]3−/4−) as a mediator in the solution. Variations in the electrochemical response of the [Fe(CN)6]3−/4− probe are observed after introducing redox inactive double-stranded DNA ions. The redox-active [Fe(CN)6]3−/4− probe serves as a scaffold to bring DNA into the graphene-modified ITO electrode surface, provoking an increase in the current and a change in the potential when the number of base pairs increases. These results are confirmed by EIS, which shows a variation in the Rct. The calibration of DPV intensity and Rct vs. DNA base pairs (bps) number were linear in the 495–607 bps range. The proposed method could replace the nucleic acid gel electrophoresis technique to determine the presence of a DNA fragment and quantify its size.

Stretching effects on non-adiabatic electron dynamic behavior in poly(dG)-poly(dC) DNA upon the proton irradiation

The electronic excitations caused by DNA when exposed to ion radiation is essential to DNA damage. In this paper, we investigated the energy deposition and electron excitation process of DNA with reasonable stretching range upon proton irradiation based on time-dependent density functional theory. Stretching changes the strength of hydrogen bonding between the DNA base pairs, which in turn affects the Coulomb interaction between the projectile and DNA. As a semi-flexible molecule, the way of energy deposition is weakly sensitive to the stretching rate of DNA. However, the increase of stretching rate causes the increase of charge density along the trajectory channel, sequentially resulting in an increase in proton resistance along the intruding channel. The Mulliken charge analysis indicates that the guanine base and guanine ribose are ionized, meanwhile the cytosine base and cytosine ribose are reduced at all stretching rates. In a few femtoseconds, there exists an electron flow passing through the guanine ribose, guanine, cytosine base and the cytosine ribose in turn. This electron flow increases electron transfer and DNA ionization, promoting the side chain damage of the DNA upon ion irradiation. Our results provide a theoretical insight for deciphering the physical mechanism of the early stage of the irradiation process, and are also of great significance for the study of particle beam cancer therapy in different biological tissues.

Molecular Spectroscopy Evidence of 1,3,5-Tris(4-carboxyphenyl)benzene Binding to DNA: Anticancer Potential along with the Comparative Binding Profile of Intercalation via Modeling Studies.

One of medicinal chemistry's top priorities is the discovery of new molecules with anticancer potential. Compounds that interact with DNA are an intriguing family of chemotherapeutic medications used to treat cancer. Studies in this area have uncovered a plethora of potential anticancer medicines, such as groove binding, alkylating, and intercalator compounds. The anticancer activity of DNA intercalators (molecules that intercalate between DNA base pairs) has drawn special interest. The current study investigated the promising anticancer drug 1,3,5-Tris(4-carboxyphenyl)benzene (H3BTB) against breast and cervical cancer cell lines. In addition, 1,3,5-Tris(4-carboxyphenyl)benzene binds to DNA by groove binding. The binding of H3BTB to DNA was found to be significant which unwinds the DNA helix. Considerable electrostatic and non-electrostatic contributions were present in the binding's free energy. The cytotoxic potential of H3BTB is effectively demonstrated by the computational study outcomes, which include molecular docking and molecular dynamics (MD) simulations. The minor groove binding for the H3BTB-DNA complex is supported by molecular docking research. This study will promote empirical investigation into the synthesis of metallic and non-metallic H3BTB derivatives and their potential use as bioactive molecules for the treatment of cancer.

Interaction of bases and base pairs with polycyclic aromatic hydrocarbons as finite size model of graphene

Interaction of DNA bases and base pairs with polycyclic aromatic hydrocarbons (PAHs) as finite size models of graphene were studied theoretically using the Density Functional Theory (DFT). The finite size PAH optimized in a plane were used as finite size models of graphene. These structures were optimized at the B3LYP, B98 and MPW1PW91 functionals of DFT along with the 6–31G(d,p) basis set. For the stability of bases and base pairs, binding energies with and without basis set superposition error (BSSE) were calculated at mentioned levels. The calculated binding energies indicates that edges of PAHs are more feasible for reactions.

Abstract 4731: Novel epigenetics technology for high-throughput processing of limited samples to study cancer using cavitation-based pixelated ultrasound and tagmentation-indexing ChIP-Seq

Abstract Epigenetics has shown great potential in translational, clinical, and precision medicine research, but with inadequate implementation. This is due to major problems with sample availability, and processing which is laborious, costly, slow, inconsistent, and leads to sample loss. Epigenetics studies need samples with certain minimum concentrations and volumes to address all necessary questions. The samples often need to be in single cell or nuclear suspensions. For chromatin immunoprecipitation (ChIP), a consistent size of approximately 300 base pairs of DNA is essential but difficult to achieve. To address the above problems, we present novel cutting-edge epigenetics methodologies. Homogenization of various tissue types from diverse patients with different disease states is the first crucial step in sample processing. Hence, we present new protocols which are compatible with high-throughput cavitation-based pixelated ultrasound sonication. It processes limited quantities of samples in a 96-well plate where cells can be grown and antibody can be coated for ChIP. Further, 1 to 12 columns of the 96-well plate can be flexibly regulated to extract lysates. Our results show how this rapid and simple technology integrates with ChIP-sequencing (seq) and RNA-seq workflows, yielding very consistent output from limited tissue samples. Bioinformatics analysis of the ChIP-seq shows the corresponding biological significance. Certain limitations of ChIP has led to the evolution of other methods but they are mostly unsuccessful in mapping transcription factors. Hence, we next present a modified ChIP-seq combined with tagmentation, indexing and pooling, coupled to pixelated ultrasound based-cavitation. Here, individual samples are placed in each well of a 96-well plate containing unique indexing adapters fused to Tn5 transposase. Hence, each sample undergoes tagmentation - a process where DNA gets fragmented and simultaneously inserted with index adapters. Next, pixelated ultrasound helps to rapidly extract the complex of protein-tagmented DNA from 96 samples which are pooled into a single tube because they are uniquely indexed, then split up for immunoprecipitation by different antibodies. Bioinformatics analysis shows that the results are robust, consistent, and match ENCODE datasets. Hence, our methods can help to process high-throughput samples for AACR Project GENIE. Overall, we present novel technology to process limited human samples for enabling epigenetics research at the clinical interface from bench to bedside. The simple and less expensive methods yield high quality samples to enable high-throughput analysis of epigenetics including transcription factors which are important in cancer. They help us to understand targeted epigenetic regulations of genes for therapeutic developments and treating cancer. Citation Format: Rwik Sen, Ngoc Tran, Sarah Traynor, Eric Maina, Jason Poole. Novel epigenetics technology for high-throughput processing of limited samples to study cancer using cavitation-based pixelated ultrasound and tagmentation-indexing ChIP-Seq. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4731.

“Helicase” activity promoted through dynamic interactions between a ssDNA translocase and a diffusing SSB protein

Replication protein A (RPA) is a eukaryotic single-stranded (ss) DNA-binding (SSB) protein that is essential for all aspects of genome maintenance. RPA binds ssDNA with high affinity but can also diffuse along ssDNA. By itself, RPA is capable of transiently disrupting short regions of duplex DNA by diffusing from a ssDNA that flanks the duplex DNA. Using single-molecule total internal reflection fluorescence and optical trapping combined with fluorescence approaches, we show that S. cerevisiae Pif1 can use its ATP-dependent 5'to 3' translocase activity to chemomechanically push a single human RPA (hRPA) heterotrimer directionally along ssDNA at rates comparable to those of Pif1 translocation alone. We further show that using its translocation activity, Pif1 can push hRPA from a ssDNA loading site into a duplex DNA causing stable disruption of at least 9 bp of duplex DNA. These results highlight the dynamic nature of hRPA enabling it to be readily reorganized even when bound tightly to ssDNA and demonstrate a mechanism by which directional DNA unwinding can be achieved through the combined action of a ssDNA translocase that pushes an SSB protein. These results highlight the two basic requirements for any processive DNA helicase: transient DNA base pair melting (supplied by hRPA) and ATP-dependent directional ssDNA translocation (supplied by Pif1) and that these functions can be unlinked by using two separate proteins.

Caffeine-induced release of small molecules from DNA nanostructures

Several planar aromatic molecules are known to intercalate between base pairs of double-stranded DNA. This mode of interaction has been used to stain DNA as well as to load drug molecules onto DNA-based nanostructures. Some small molecules are also known to induce deintercalation in double-stranded DNA, one such molecule being caffeine. Here, we compared the ability of caffeine to cause deintercalation of ethidium bromide, a representative DNA intercalator, from duplex DNA and three DNA motifs of increasing structural complexity (four-way junction, double crossover motif, and DNA tensegrity triangle). We found that caffeine impedes the binding of ethidium bromide in all these structures to the same extent, with some differences in deintercalation profiles. Our results can be useful in the design of DNA nanocarriers for intercalating drugs, where drug release can be chemically stimulated by other small molecules.

Interaction of an anticancer benzopyrane derivative with DNA: Biophysical, biochemical, and molecular modeling studies

BackgroundSIMR1281 is a potent anticancer lead candidate with multi- target activity against several proteins; however, its mechanism of action at the molecular level is not fully understood. Revealing the mechanism and the origin of multitarget activity is important for the rational identification and optimization of multitarget drugs. MethodsWe have used a variety of biophysical (circular dichroism, isothermal titration calorimetry, viscosity, and UV DNA melting), biochemical (topoisomerase I & II assays) and computational (molecular docking and MD simulations) methods to study the interaction of SIMR1281 with duplex DNA structures. ResultsThe biophysical results revealed that SIMR1281 binds to dsDNA via an intercalation-binding mode with an average binding constant of 3.1 × 106 M−1. This binding mode was confirmed by the topoisomerases' inhibition assays and molecular modeling simulations, which showed the intercalation of the benzopyrane moiety between DNA base pairs, while the remaining moieties (thiazole and phenyl rings) sit in the minor groove and interact with the flanking base pairs adjacent to the intercalation site. ConclusionsThe DNA binding characteristics of SIMR1281, which can disrupt/inhibit DNA function as confirmed by the topoisomerases' inhibition assays, indicate that the observed multi-target activity might originate from ligand intervention at nucleic acids level rather than due to direct interactions with multiple biological targets at the protein level. General significanceThe findings of this study could be helpful to guide future optimization of benzopyrane-based ligands for therapeutic purposes.

Metal-Mediated DNA Nanotechnology in 3D: Structural Library by Templated Diffraction.

DNA double helices containing metal-mediated DNA (mmDNA) base pairs have been constructed from Ag+ and Hg2+ ions between pyrimidine:pyrimidine pairs with the promise of nanoelectronics. Rational design of mmDNA nanomaterials has been impractical without a complete lexical and structural description. Here, we explore the programmability of structural DNA nanotechnology toward its founding mission of self-assembling a diffraction platform for biomolecular structure determination. We employed the tensegrity triangle to build a comprehensive structural library of mmDNA pairs via X-ray diffraction and elucidated generalized design rules for mmDNA construction. We uncovered two binding modes: N3-dominant, centrosymmetric pairs and major groove binders driven by 5-position ring modifications. Energy gap calculations showed additional levels in the lowest unoccupied molecular orbitals (LUMO) of mmDNA structures, rendering them attractive molecular electronic candidates. This article is protected by copyright. All rights reserved.

Electrochemical detection of the oxidative damage of a potential pyrimido[5,4-g]pteridine-derived antitumor agent toward DNA.

In this work, we design and synthesize 2,2'-(7,9-dimethyl-2,4,6,8-tetraoxo-6,7,8,9-tetrahydropyrimido[5,4-g]pteridine-1,3(2H,4H)-diyl)bis(N,N-bis(2-chloroethyl)acetamide) (PT-MCA) as a novel DNA intercalator and potential antitumor agent. Electrochemical analysis reveals the redox process of PT-MCA on the electrode surface. The bioelectrochemical sensors are obtained by modifying the surface of GCE with calf thymus DNA (ctDNA), poly (dG), poly (dA), and G-quadruplex, respectively. The DNA oxidative damage induced by PT-MCA is investigated by comparing the peak intensity change of dGuo and dAdo and monitoring the peaks of the oxidation products of guanine and/or adenine (8-oxoGua and/or 2,8-oxoAde). UV-vis absorption and fluorescence spectra and gel electrophoresis are further employed to understand the intercalation of PT-MCA into DNA base pairs. Moreover, PT-MCA is proved to exhibit stronger anti-proliferation activity than mitoxantrone against both 4T1 and B16-F10 cancer cells. At last, the oxidative damage of PT-MCA toward ctDNA is not interfered by the coexistence of ions and also can be detected in real serums.

Base Pair Stacking Modulates Solid-State Charge Transport in DNA Hairpins.

Particular interest has been focused on modulation of solid-state charge transport (CT) in DNA. Nevertheless, it remains challenging to do so in a sensitive and predictive manner due to the lack of a definite relationship between DNA base pair stacking and DNA CT. The challenges can be mainly attributed to the ill-defined systems, which may lead to ambiguous and even contradictory conclusions. Here, we use DNA hairpins to construct the well-defined self-assembled monolayers. We reveal nearly positive-linear correlations between DNA conformation and CT in the DNA hairpins regulated with metal ion chelation and DNA sequence. The correlations have been confirmed by the solid-state current-voltage characteristics and circular dichroism in solution. The enhanced CT via metal ion chelated DNA hairpins is mainly from the improved DNA energy coupling to electrodes, not the almost unchanged energy barrier when Hg ion-induced DNA conformational switches toward the canonical B-form.

Analytical and therapeutic profiles of DNA methylation alterations in cancer; an overview of changes in chromatin arrangement and alterations in histone surfaces.

DNA methylation is the most important epigenetic element that activates the inhibition of gene transcription and is included in the pathogenesis of all types of malignancies. Remarkably, the effectors of DNA methylation are DNMTs (DNA methyltransferases) that catalyze denovo or keep methylation of hemimethylated DNA after the DNA replication process. DNA methylation structures incancer are altered, with three procedures by which DNA methylation helps cancer development which are including direct mutagenesis, hypomethylation of the cancer genome, and also focal hypermethylation of the promoters of TSGs (tumor suppressor genes). Conspicuously, DNA methylation, nucleosome remodeling, RNA-mediated targeting, and histone modification balance modulate many biological activities that are essential and indispensable to the genesis of cancer and also can impact many epigenetic changes including DNA methylation and histone modifications as well as adjusting of non-coding miRNAs expression in prevention and treatment of many cancers. Epigenetics points to heritable modifications in gene expression that do not comprise alterations in the DNA sequence. The nucleosome is the basic unit of chromatin, consisting of 147 base pairs (bp) of DNA bound around a histone octamer comprised of one H3/H4 tetramer and twoH2A/H2B dimers. DNA methylation is preferentially distributed over nucleosome regions and is less increased over flanking nucleosome-depleted DNA, implying a connection between nucleosome positioning and DNA methylation. In carcinogenesis, aberrations in the epigenome may also include in the progression of drug resistance. In this report, we report the rudimentary notes behind these epigenetic signaling pathways and emphasize the proofs recommending that their misregulation can conclude in cancer. These findings in conjunction with thepromising preclinical and clinical consequences observed with epigenetic drugs against chromatin regulators, confirm the important role of epigenetics in cancer therapy.