Supercoiled Form Research Articles

Ultra-low-energy (

Since ion energy deposition in the ion-bombarded materials dominantly occurs in the low-energy range, it is very interesting to know effects from ultra-low-energy ion interaction with DNA for understanding ion-beam-induced genetic mutation. Tens-keV Ar- and N-ion beams were decelerated to ultra-low energy ranging from 20 to 100eV, or only a few to 10eV/u, to bombard naked plasmid DNA. The bombarded DNA was analyzed using gel electrophoresis for DNA form changes. The original DNA supercoiled form was found to change to relaxed and linear forms, indicating single or double strand breaks after bombarded by tens-eV ion beam. N-ion beam was found more effective in inducing DNA change and mutation than Ar-ion beam. The study demonstrated that the ion bombardment with energy as low as several-tens eV was able to break DNA strands and thus potentially to cause genetic modification of biological cells. The experimental results were discussed in terms of direct atomic collision between the ions and DNA atoms.

Square Planar Platinum(II) Complexes with N,S-Donor Ligands: Synthesis, Characterisation, DNA Interaction and Cytotoxic Activity

The platinum(II) complexes with N,S-donor ligand have been synthesised and characterised by physiological techniques like elemental, electronic, Fourier transform infrared, hydrogen-1 nuclear magnetic resonance ((1)H NMR) and liquid chromatography-mass spectrometry spectra. The synthesised complexes have been checked for their DNA binding ability by absorption titration and viscosity measurement, and the results show that the complexes binds to herring sperm DNA (HS DNA) via covalent mode of binding. The DNA cleavage activity of synthesised complexes has been carried out by gel electrophoresis experiment using supercoiled form of pUC19 DNA, showing the unwinding of the negatively charged supercoiled DNA. Brine shrimp (Artemia cysts) lethality bioassay technique has been applied for the determination of toxic property of synthesised complexes in terms of micromolars.

Synthesis, Characterisation, Interaction with DNA, Cytotoxicity, and Apoptotic Studies of Ruthenium(II) Polypyridyl Complexes

We report the synthesis and characterisation of two new ruthenium(ii) polypyridyl complexes containing monodentate ancillary ligands [Ru(L)4(4HEPIP)], where L = 4-aminopyridine (1) or pyridine (2) and 4HEPIP = 2-(4-hydroxy-3-ethoxyphenyl)-1H-imidazo[4,5-f][1,10](phenanthroline). These complexes were characterised by elemental analysis and ultraviolet-visible, infrared, and 1H NMR spectroscopy. The binding properties of the two complexes towards calf thymus (CT)-DNA were investigated with different spectrophotometric methods, viscosity measurements, and salt dependent studies. Experimental results indicated that the complexes interact with CT-DNA base pairs by intercalation. Upon irradiation at 365 nm, these complexes efficiently cleave pBR322 DNA from super coiled form I to nicked form II. Their cytotoxicity on different cancer cell lines such as A549, Du145, and HeLa was investigated. The IC50 values are 39.5, 28.3, and 27.3 μM for complex 1, and 55, 67.9, and 47.9 μM for complex 2 respectively. Cellular uptake and apoptosis induced by these complexes was also studied.

Studies of DNA-Binding and DNA-Cutting Mechanism of an Azamacrocyclic Cerium Complex with Carboxyl Branch

An azamacrocyclic compound with a carboxyl branch, 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclo-tetradecane- N/-acetic acid (L), and its cerium complex were synthesised and characterised. The mode of combination of the cerium complex with DNA was investigated by fluorescence and UV-Vis absorption spectroscopy. The cutting function of the cerium complex towards supercoiled DNA was studied by the gel electrophoresis method. The results show that metal complex can bind to the phosphate group of DNA double helix and promote the hydrolysis of the phosphodiester bond of supercoiled DNA (Form I); under certain conditions, supercoiled form DNA (Form I) was transformed into the nicked form DNA (Form II) under the strong cutting effect of the macrocyclic cerium complex; the cutting is completed by a hydrolysis mechanism.

Synthesis, Characterization, DNA Binding Studies, Photocleavage, Cytotoxicity and Docking Studies of Ruthenium(II) Light Switch Complexes

A new ligand 3-(1H-imidazo[4,5-f][1,10]phenanthrolin-2yl)phenylboronic acid and its (IPPBA) three ruthenium(II) complexes [Ru(phen)2(IPPBA)](ClO4)2 (1), [Ru(bpy)2(IPPBA)](ClO4)2 (2) and [Ru(dmb)2(IPPBA)](ClO4)2 (3) have been synthesized and characterized by elemental analysis, UV/VIS, IR, (1)H-NMR,(13)C-NMR and mass spectra. The binding behaviors of the three complexes to calf thymus DNA were investigated by absorption spectra, emission spectroscopy, viscosity measurements, thermal denaturation and photoactivated cleavage. The DNA-binding constants for complexes 1, 2 and 3 have been determined to be 7.9 × 10(5) M(-1), 6.7 × 10(5) M(-1) and 2.9 × 10(5) M(-1). The results suggest that these complexes bound to double-stranded DNA in an intercalation mode. Upon irradiation at 365 nm, three ruthenium complexes were found to promote the cleavage of plasmid pBR322 DNA from super coiled form І to nicked form ІІ. Further in the presence of Co(2+), the emission of DNA-Ru(ΙΙ) complexes can be quenched. And when EDTA was added, the emission was recovered. The experimental results show that all three complexes exhibited the "on-off-on" properties of molecular "light switch". The highest Cytotoxicity potential of the complex1 was observed on the Human alveolar adenocarcinoma (A549) cell line. Good agreement was generally found between the spectroscopic techniques and molecular docked model which provides further evidence of groove binding.

Synthesis of new calix[4]arene amide derivatives and investigation of their DNA cleavage activity

This study comprises the synthesis of new p-tert-butylcalix[4]arene with different amide functional groups and summarises an investigation of their DNA cleavage activities. The structural investigations of the synthesised compounds were examined by FTIR, 1H NMR, 13C NMR, elemental analysis and FAB-MS techniques. The interaction between these compounds and pBR322 plasmid DNA has been investigated via agarose gel electrophoresis and, according to the results, compounds 5, 7, 8 and 13 exhibit efficient DNA cleavage activity. In the electrophoresis images of 5, 7 and 8, Form IV which is small DNA fragment was observed in addition to supercoiled Form I, open circular Form II and linear Form III.

Highly efficient synthetic iron-dependent nucleases activate both intrinsic and extrinsic apoptotic death pathways in leukemia cancer cells

The nuclease activity and the cytotoxicity toward human leukemia cancer cells of iron complexes, [Fe(HPClNOL)Cl2]NO3 (1), [Cl(HPClNOL)Fe(μ-O)Fe(HPClNOL)Cl]Cl2·2H2O (2), and [(SO4)(HPClNOL)Fe(μ-O)Fe(HPClNOL)(SO4)]·6H2O (3) (HPClNOL=1-(bis-pyridin-2-ylmethyl-amino)-3-chloropropan-2-ol), were investigated. Each complex was able to promote plasmid DNA cleavage and change the supercoiled form of the plasmid to circular and linear ones. Kinetic data revealed that (1), (2) and (3) increase the rate of DNA hydrolysis about 278, 192 and 339million-fold, respectively. The activity of the complexes was inhibited by distamycin, indicating that they interact with the minor groove of the DNA. The cytotoxic activity of the complexes toward U937, HL-60, Jukart and THP-1 leukemia cancer cells was studied employing 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), fluorescence and electronic transmission microscopies, flow cytometry and a cytochrome C release assay. Compound (2) has the highest activity toward cancer cells and is the least toxic for normal ones (i.e. peripheral blood mononuclear cells (PBMCs)). In contrast, compound (1) is the least active toward cancer cells but displays the highest toxicity toward normal cells. Transmission electronic microscopy indicates that cell death shows features typical of apoptotic cells, which was confirmed using the annexin V-FITC/PI (fluorescein isothiocyanate/propidium iodide) assay. Furthermore, our data demonstrate that at an early stage during the treatment with complex (2) mitochondria lose their transmembrane potential, resulting in cytochrome C release. A quantification of caspases 3, 9 (intrinsic apoptosis pathway) and caspase 8 (extrinsic apoptosis pathway) indicated that both the intrinsic (via mitochondria) and extrinsic (via death receptors) pathways are involved in the apoptotic stimuli.

Radioprotective role of clinical drug diclofenac sodium

The potential of clinical drug diclofenac sodium which is routinely used in clinics as non-steroid anti-inflammatory drugs opens a new insight in development of radioprotector. The drug has shown its potential radioprotective efficacy in clonogenic cell survival in Chinese hamster V79 cells with a DMF of 1.4. The pBR322 plasmid DNA gets damaged by radiation in which the supercoiled form gradually disappears with increasing radiation dose. Diclofenac sodium has shown its radioprotective potential by scavenging radiation induced free radicals which are depicted by its ability in restoring the fraction of supercoiled form of plasmid DNA back to normal. 250μM concentration of the drug provides GSSB yield of 3.65±0.5×10−9Da−1Gy−1. This drug has shown to have a free radical scavenging activity because the radical cation with blue color is converted to the colorless neutral form by addition of diclofenac sodium in ABTS assay. Whole body survival study has shown it to protect 45.5% of C57BL/6 mice at a lethal irradiation dose of 9Gy. Therefore, this molecule offers a potential radioprotective ability besides being used routinely as analgesic and anti inflammatory compound.

DNA-binding and cleavage, cytotoxicity properties of Ru(II) complexes with 2-(4′-chloro-phenyl) imidazo[4,5-f][1,10]phenanthroline, ligand and their “light switch” on–off effect

Three new complexes of the type [Ru(phen)2PIP-Cl](1) [Ru(bpy)2PIP-Cl](2) and [Ru(dmp)2PIP-Cl](3) (phen = 1,10-phenanthroline; bpy = 2,2′-bipyridine; dmb = 4,4-dimethyl-2,2′-bipyridine), PIP-Cl = 2-(4′-chloro-phenyl) imidazo[4,5-f][1,10]phenanthroline) were synthesized and characterized by using UV–VIS, IR and 1H-NMR, 13C-NMR spectral methods. Absorption spectroscopy, emission spectroscopy, viscosity measurements and DNA melting techniques were used to investigate the binding of these Ru(II) complexes with calf thymus DNA, and photocleavage studies were used to investigate the binding of these complexes with plasmid DNA. The spectroscopic studies together with viscosity measurements and DNA melting studies supported fact that Ru(II) complexes bind to CT-DNA(calf thymus DNA) by an intercalation mode via PIP-Cl into the base pairs of DNA. Upon irradiation, these novel Ru(II) complexes cleave the plasmid pBR 322 DNA from the supercoiled form I to the open circular form II.

Therapeutic low-intensity red laser for herpes labialis on plasmid survival and bacterial transformation

A low-intensity laser is used in treating herpes labialis based on the biostimulative effect, albeit the photobiological basis is not well understood. In this work experimental models based on Escherichia coli cultures and plasmids were used to evaluate effects of low-intensity red laser on DNA at fluences for treatment of herpes labialis. To this end, survival and transformation efficiency of plasmids in E. coli AB1157 (wild type), BH20 (fpg/mutM(-)) and BW9091 (xthA(-)), content of the supercoiled form of plasmid DNA, as well as nucleic acids and protein content from bacterial cultures exposed to the laser, were evaluated. The data indicate low-intensity red laser: (i) alters the survival of plasmids in wild type, fpg/mutM(-) and xthA(-)E. coli cultures depending of growth phase, (ii) alters the content of the supercoiled form of plasmids in the wild type and fpg/mutM(-)E. coli cells, (iii) alters the content of nucleic acids and proteins in wild type E. coli cells, (iv) alters the transformation efficiency of plasmids in wild type and fpg/mutM(-)E. coli competent cells. These data could be used to understand positive effects of low-intensity lasers on herpes labialis treatment.

Supercoiled and linear plasmid DNAs interactions with methylene blue

Slow accumulation of plasmids from their diluted, pg/mL solutions (pH4.7) on a well defined glassy carbon (GC) electrode surface allowed for the formation of stable electrode layers consisting of two types of plasmid DNAs — pUC19 and pGEX-4T-2, in two forms — supercoiled circular (sc) and linear (lin). In the presence of methylene blue (MB), a typical redox indicator, the oxidation signals of nucleic acid bases are significantly enhanced. The interactions of the plasmids with MB are tested and used to distinguish between various types of plasmids. Instead of an MB reduction signal at ca. −0.2V vs. SCE, typically used to study MB interactions with DNAs, we have used the corresponding oxidation signal at ca. −0.2V, MB(I), as well as another oxidation signal at 1.05V, MB(III). On a bare GC electrode, the MB(III) and MB(I) signals are proportional to each other, while in the presence of the plasmid DNAs the relations between MB(III) and MB(I) depend on the type of plasmid. The plots: MB(III)/MB(I) vs. [MB] and MB(I) potential shift vs. [MB] are used to distinguish between the supercoiled and linear forms of the pUC19 and pGEX-4T-2 plasmids.

Noncoding DNA in Lipofection of HeLa Cells—A Few Insights

In cationic carrier-mediated gene delivery, the disproportional relationship between the quantity of delivered DNA and the amount of encoded protein produced is a well-known phenomenon. The numerous intracellular barriers which need to be overcome by pDNA to reach the nucleoplasm play a major role in it. In contrast to what one would expect, a partial replacement of coding pDNA by noncoding DNA does not lead to a decrease in transfection efficiency. The mechanism underlying this observation is still unclear. Therefore, we investigated which constituents of the transfection process might contribute to this phenomenon. Our data reveal that the topology of the noncoding plasmid DNA plays a major role. Noncoding pDNA can be used only in a supercoiled form to replace coding pDNA in Lipofectamine lipoplexes, without a loss in transfection levels. When noncoding pDNA is linearized or partly digested, it diminishes the transfection potential of coding pDNA, as does noncoding salmon DNA. The difference in transfection efficiencies could not be attributed to diverse physicochemical characteristics of the Lipofectamine lipoplexes containing different types of noncoding DNA or to the extent of their internalization. At the level of endosomal release, however, nucleic acid release from the endosomal compartment proceeds faster when lipoplexes contain noncoding salmon DNA. Since the half-life of pDNA in the cytosol hardly exceeds 90 min, it is conceivable that prolonged release of coding pDNA from complexes carrying supercoiled noncoding pDNA may explain its positive effect on transfection, while this depot effect does not exist when noncoding salmon DNA is used.

An ion beam deceleration lens for ultra-low-energy ion bombardment of naked DNA

Study of low-energy ion bombardment effect on biological living materials is of significance. High-energy ion beam irradiation of biological materials such as organs and cells has no doubt biological effects. However, ion energy deposition in the ion-bombarded materials dominantly occurs in the low-energy range. To investigate effects from very-low-energy ion bombardment on biological materials, an ion beam deceleration lens is necessary for uniform ion energy lower than keV. A deceleration lens was designed and constructed based on study of the beam optics using the SIMION program. The lens consisted of six electrodes, able to focus and decelerate primary ion beam, with the last one being a long tube to obtain a parallel uniform exiting beam. The deceleration lens was installed to our 30-kV bioengineering-specialized ion beam line. The final decelerated-ion energy was measured using a simple electrostatic field to bend the beam to range from 10eV to 1keV controlled by the lens parameters and the primary beam condition. In a preliminary test, nitrogen ion beam at 60eV decelerated from a primary 20-keV beam bombarded naked plasmid DNA. The original DNA supercoiled form was found to change to relaxed and linear forms, indicating single or double strand breaks. The study demonstrated that the ion bombardment with energy as low as several-tens eV was possible to break DNA strands and thus potential to cause genetic modification of biological cells.

Metal-Based Biologically Active Compounds: Synthesis, Characterization, DNA Interaction, Antibacterial, Cytotoxic and SOD Mimic Activities

The square pyramidal copper(II) complexes of N, O- donor ligand and ciprofloxacin have been synthesized. Synthesized complexes were characterized by physicochemical parameters like elemental analysis, electronic, FT-IR and LC-MS spectra. The complexes were screened for their antimicrobial activity against Gram(+Ve), i.e. Staphylococcus aureus, Bacillus subtilis, and Gram(-Ve), i.e. Serratia marcescens, Pseudomonas aeruginosa and Escherichia coli, microorganisms in terms of minimum inhibitory concentration and colony-forming unit. To determine the binding mode of complexes with Herring Sperm DNA, absorption titration and viscosity measurement were employed. DNA cleavage activity was carried out by gel electrophoresis experiment using supercoiled form of pUC19 DNA. The complexes were tested for their superoxide dismutase mimic activity in terms of IC(50) value. Synthesized complexes were also screened for their cytotoxicity using brine shrimp lethality assay method.

1831 – Dnase and protease activity of immunoglobulins G of patients with schizophrenia

Introduction Phenomenon of presence of catalytic properties in immunoglobulins has been actively investigated. Research of catalytic properties of antibodies in schizophrenic patients with various clinical manifestations of the illness has not been carried out previously. Objectives To study DNase and proteolytic activity of immunoglobulins G isolated from serum of blood of patients with schizophrenia. Methods IgG have been isolated from serum of blood of 34 persons with affine chromatography. DNase activity of antibodies was identified according to degree of hydrolysis of supercoiled form of DNA of plasmid pBluescript per unit of time. Proteolytic activity was assessed according to degree of hydrolysis of basic protein myelin and its peptides. IgG were electrophoretic homogeneity. Results We have identified that IgG of schizophrenic patients possess a higher (0,392 ± 0,19 nM DNA /mgAB/h), than in healthy persons (0,029 ± 0,06 nM DNA /mgAB/h) specific DNAse activity. It has been shown that DNase activity is an own property of antibodies. It has been found that proteolytic hydrolysis of serum of blood of schizophrenic patients is 5 times as high as indices of hydrolysis in healthy persons. It has been revealed that patients with predominant negative symptoms show maximum high percent of protease hydrolysis 66,9%, different from patients with leading positive symptoms (13,9%). Conclusions Increase of DNA-hydrolyzing properties of Ig G is likely to be associated with great number of extracellular DNA. Detection of high values of proteolytic activity may be associated with occurring in serum of blood of patients of large number of destructed or damaged proteins.

Single step plasmid DNA purification using methacrylate monolith bearing combination of ion-exchange and hydrophobic groups

Purification of high quantities of human grade plasmid DNA is one of the most intensive production steps. Because of that several methods have been proposed, among them also chromatographic purification using methacrylate monoliths. Recently, a process comprising the combination of hydrophobic interaction (HIC) monolith and ion-exchange monolith was developed. In this work both chemistries were tried to be introduced on a single monolith. Methacrylate monoliths bearing octylamine groups, combination of butyl (C4) grafted methacrylate groups and diethylaminoethyl (DEAE) groups as well as grafted chains bearing both C4 and DEAE groups were prepared. All monoliths were investigated for their ionic and protein capacity and compared to conventional epoxy, C4, and DEAE methacrylate monoliths. Octylamine monolith and monolith bearing combination of C4 grafted methacrylate groups and DEAE groups were found to be the most promising candidates and were further tested for plasmid DNA (pDNA) dynamic binding capacity under ion-exchange (IEX) and HIC binding conditions and ability to separate open circular (OC) from supercoiled (SC) pDNA forms and RNA from pDNA. Since monolith bearing combination of grafted C4 methacrylate groups and DEAE groups was superior in all three tested features, exhibiting pDNA dynamic binding capacity of 4.7mg/ml under IEX conditions and 2.1mg/ml under HIC conditions, it was used for the development of a single step purification method and tested with pure pDNA as well as with cell lysate. Developed method removed over 99% of RNA, host cell proteins (HCP) and genomic DNA (gDNA) demonstrating capacity to purify around 1.5mg ofpDNA/ml of monolith from cell lysate.

K(+) , Na(+) , and Mg(2+) on DNA translocation in silicon nitride nanopores.

In this work, we report on how salt concentration and cation species affect DNA translocation in voltage-biased silicon nitride nanopores. The translocation of dsDNA in linear, circular, and supercoiled forms was measured in salt solutions containing KCl, NaCl, and MgCl(2) . As the KCl concentrations were decreased from 1 to 0.1 M, the time taken by a DNA molecule to pass through a nanopore was shorter and the frequency of the translocation in a folded configuration was reduced, suggesting an increase in DNA electrophoretic mobility and DNA persistence length. When the salt concentration was kept at 1 M, but replacing K(+) with Na(+) , longer DNA translocation times (t(d) ) were observed. The addition of low concentrations of MgCl(2) with 1.6 M KCl resulted in longer t(d) and an increased frequency of supercoiled DNA molecules in a branched form. These observations were consistent with the greater counterion charge screening ability of Na(+) and Mg(2+) as compared to K(+) . In addition, we demonstrated that dsDNA molecules indeed translocated through a ∼10 nm nanopore by PCR amplification and gel electrophoresis. We also compared the dependence of DNA mobility and conformation on KCl concentration and cation species measured at single molecule level by silicon nitride nanopores with existing bulk-based experimental results and theoretical predictions.

Square planar palladium(II) complexes of bipyridines: synthesis, characterization, and biological studies

A series of square planar mononuclear palladium(II) complexes, [Pd(L n )(OMe)2] (where L n = 4-(4-chlorophenyl)-6-phenyl-2,2′-bipyridine, 4,6-bis(4-chlorophenyl)-2,2′-bipyridine, 4-(4-bromophenyl)-6-(4-chlorophenyl)-2,2′-bipyridine, and 6-(4-chlorophenyl)-4-p-tolyl-2,2′-bipyridine), have been synthesized and characterized. Interaction of palladium complexes with DNA has been investigated by electronic absorption spectra, viscosity measurements and DNA melting temperature techniques. The metal complex-DNA interaction produced hypochromism and bathochromism, suggesting intercalative binding. Viscosity data support the intercalation mode of binding. Palladium(II) complexes promote cleavage of plasmid pUC19 DNA from the supercoiled form to the open circular form. Antibacterial activities of the complexes have also been evaluated against five pathogenic bacteria. The antimicrobial test results reveal that all compounds have good antibacterial activity against both Gram(−ve) and Gram(+ve) bacterial species compared to the ligands and metal salt.

Synthesis, characterization and biological studies of mononuclear copper(II) complexes with ciprofloxacin and N, O donor ligands

Abstract The mixed ligand Cu(II) complexes of ciprofloxacin and N, O donor Schiff bases have been prepared and characterized by physicochemical techniques. In these complexes, ciprofloxacin acts as bidentate deprotonated ligand bound to the metal through the pyridone oxygen and one carboxylate oxygen. The antimicrobial activity of the complexes has been tested on three Gram(− ve) and two Gram(+ ve) microorganisms in terms of minimum inhibitory concentration (MIC) and colony forming unit (CFU). The interaction study of the complexes with Herring Sperm DNA (HS-DNA) has been performed by absorption titration and viscosity measurement. The DNA cleavage activity has been carried out by gel electrophoresis experiment using supercoiled form of pUC19 DNA. Potential cytotoxic effect of complexes has been investigated by brine shrimp lethality assay method. The complexes have been also screened for their enzymatic behaviour in terms of IC 50 value.

YY1-binding sites provide central switch functions in the PARP-1 gene expression network.

Evidence is presented for the involvement of the interplay between transcription factor Yin Yang 1 (YY1) and poly(ADP-ribose) polymerase-1 (PARP-1) in the regulation of mouse PARP-1 gene (muPARP-1) promoter activity. We identified potential YY1 binding motifs (BM) at seven positions in the muPARP-1 core-promoter (−574/+200). Binding of YY1 was observed by the electrophoretic supershift assay using anti-YY1 antibody and linearized or supercoiled forms of plasmids bearing the core promoter, as well as with 30 bp oligonucleotide probes containing the individual YY1 binding motifs and four muPARP-1 promoter fragments. We detected YY1 binding to BM1 (−587/−558), BM4 (−348/−319) and a very prominent association with BM7 (+86/+115). Inspection of BM7 reveals overlap of the muPARP-1 translation start site with the Kozak sequence and YY1 and PARP-1 recognition sites. Site-directed mutagenesis of the YY1 and PARP-1 core motifs eliminated protein binding and showed that YY1 mediates PARP-1 binding next to the Kozak sequence. Transfection experiments with a reporter gene under the control of the muPARP-1 promoter revealed that YY1 binding to BM1 and BM4 independently repressed the promoter. Mutations at these sites prevented YY1 binding, allowing for increased reporter gene activity. In PARP-1 knockout cells subjected to PARP-1 overexpression, effects similar to YY1 became apparent; over expression of YY1 and PARP-1 revealed their synergistic action. Together with our previous findings these results expand the PARP-1 autoregulatory loop principle by YY1 actions, implying rigid limitation of muPARP-1 expression. The joint actions of PARP-1 and YY1 emerge as important contributions to cell homeostasis.