DNA transitions induced by binding of PARP‐1 to cruciform structures in supercoiled plasmids

Chasovskikh, Sergey; Dimtchev, Alexandre; Smulson, Mark E.; Dritschilo, Anatoly

doi:10.1002/cyto.a.20187

Cited by 38 publications

(29 citation statements)

References 38 publications

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“…It occurs by heteromodification of histones, which promotes the decondensation of high order chromatin, and by binding to enhancer/promoter regulatory cis-elements (44). Previous studies have reported that PARP-1 recognizes unusual DNA conformations such as hairpins/cruciforms (47)(48)(49) and the G-quadruplex formed by a cis-element in the human KRAS promoter (8). Interestingly, Ladame and co-workers (50) have shown that PARP-1 undergoes automodification after binding to the c-kit quadruplex.…”

Section: Discussionmentioning

confidence: 99%

The KRAS Promoter Responds to Myc-associated Zinc Finger and Poly(ADP-ribose) Polymerase 1 Proteins, Which Recognize a Critical Quadruplex-forming GA-element

Cogoi

Paramasivam

Membrino

et al. 2010

Journal of Biological Chemistry

129

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The murine KRAS promoter contains a G-rich nuclease hypersensitive element (GA-element) upstream of the transcription start site that is essential for transcription. Pulldown and chromatin immunoprecipitation assays demonstrate that this GA-element is bound by the Myc-associated zinc finger (MAZ) and poly(ADP-ribose) polymerase 1 (PARP-1) proteins. These proteins are crucial for transcription, because when they are knocked down by short hairpin RNA, transcription is downregulated. This is also the case when the poly(ADP-ribosyl)ation activity of PARP-1 is inhibited by 3,4-dihydro-5-[4-(1-piperidinyl) butoxyl]-1(2H) isoquinolinone. We found that MAZ specifically binds to the duplex and quadruplex conformations of the GA-element, whereas PARP-1 shows specificity only for the G-quadruplex. On the basis of fluorescence resonance energy transfer melting and polymerase stop assays we saw that MAZ stabilizes the KRAS quadruplex. When the capacity of folding in the GA-element is abrogated by specific G 3 T or G 3 A point mutations, KRAS transcription is down-regulated. Conversely, guanidine-modified phthalocyanines, which specifically interact with and stabilize the KRAS G-quadruplex, push the promoter activity up to more than double. Collectively, our data support a transcription mechanism for murine KRAS that involves MAZ, PARP-1 and duplex-quadruplex conformational changes in the promoter GA-element.Guanine-rich sequences have the potential to fold into intramolecular G-quadruplex (or G4-DNA) structures that are stabilized by planar arrays of four guanines paired by Hoogsteen hydrogen bonds (G-tetrad) (1). Quadruplex-forming sequences (QFS) 2 are present in prokaryotic and eukaryotic genomes, promoter regions, micro-and mini-satellite repeats, telomeres, rDNA, and the vertebrate immunoglobulin heavy chain switch regions (2). Recent bioinformatic search analyses have shown a surprisingly high presence in the human genome of QFS, on the order of 3-4 ϫ 10 5 (3, 4). The gene distribution of QFS is highly skewed because tumor suppressor genes have a very low level of QFS, whereas proto-oncogenes have a high level of such sequences (5). There seems to be a correlation between QFS and genomic instability; a low level of QFS in tumor suppressor genes is associated with genomic stability, and a high level is associated with genomic instability (5). Furthermore, the observation that QFS are often located in the region surrounding the transcription start sites of the genes and within cis-elements suggests that they may be involved in transcription regulation. This hypothesis has been formulated for a number of genes including CMYC, KRAS, C-MYB, VEGF, PDGFA, CKIT, and human insulin (6 -13). The best studied G-rich sequence folding into a G-quadruplex, whose function has been correlated with a mechanism of transcription regulation, is the one found in the promoter of the CMYC gene (6). Upstream of the P1 promoter, controlling about 80% of transcription, there is a QFS that can fold into a G-quadruplex. When this quadruplex is d...

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Section: Discussionmentioning

confidence: 99%

The KRAS Promoter Responds to Myc-associated Zinc Finger and Poly(ADP-ribose) Polymerase 1 Proteins, Which Recognize a Critical Quadruplex-forming GA-element

Cogoi

Paramasivam

Membrino

et al. 2010

Journal of Biological Chemistry

129

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“…Binding reactions were carried out with 0.1 M 497L RNA and 0.5 M HDAg-160 for 5 min at 37°C in 80 mM NaCl, 10 mM Tris, pH 7.5. Freshly cleaved muscovite mica was incubated in a mixture of a 1-(3-aminopropyl)silatrane (APS) solution for 30 min to prepare APS-mica as described previously (34). Sample droplets (5 l) were deposited on APS-mica for 2 min and then washed with deionized water and dried with nitrogen gas.…”

Section: Methodsmentioning

confidence: 99%

Hepatitis Delta Antigen Requires a Flexible Quasi-Double-Stranded RNA Structure To Bind and Condense Hepatitis Delta Virus RNA in a Ribonucleoprotein Complex

Griffin

Chasovskikh

Dritschilo

et al. 2014

J Virol

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The circular genome and antigenome RNAs of hepatitis delta virus (HDV) form characteristic unbranched, quasi-doublestranded RNA secondary structures in which short double-stranded helical segments are interspersed with internal loops and bulges. The ribonucleoprotein complexes (RNPs) formed by these RNAs with the virus-encoded protein hepatitis delta antigen (HDAg) perform essential roles in the viral life cycle, including viral replication and virion formation. Little is understood about the formation and structure of these complexes and how they function in these key processes. Here, the specific RNA features required for HDAg binding and the topology of the complexes formed were investigated. Selective 2=OH acylation analyzed by primer extension (SHAPE) applied to free and HDAg-bound HDV RNAs indicated that the characteristic secondary structure of the RNA is preserved when bound to HDAg. Notably, the analysis indicated that predicted unpaired positions in the RNA remained dynamic in the RNP. Analysis of the in vitro binding activity of RNAs in which internal loops and bulges were mutated and of synthetically designed RNAs demonstrated that the distinctive secondary structure, not the primary RNA sequence, is the major determinant of HDAg RNA binding specificity. Atomic force microscopy analysis of RNPs formed in vitro revealed complexes in which the HDV RNA is substantially condensed by bending or wrapping. Our results support a model in which the internal loops and bulges in HDV RNA contribute flexibility to the quasi-double-stranded structure that allows RNA bending and condensing by HDAg. IMPORTANCE RNA-protein complexes (RNPs) formed by the hepatitis delta virus RNAs and protein, HDAg, perform critical roles in virus replication.Neither the structures of these RNPs nor the RNA features required to form them have been characterized. HDV RNA is unusual in that it forms an unbranched quasi-double-stranded structure in which short base-paired segments are interspersed with internal loops and bulges. We analyzed the role of the HDV RNA sequence and secondary structure in the formation of a minimal RNP and visualized the structure of this RNP using atomic force microscopy. Our results indicate that HDAg does not recognize the primary sequence of the RNA; rather, the principle contribution of unpaired bases in HDV RNA to HDAg binding is to allow flexibility in the unbranched quasi-double-stranded RNA structure. Visualization of RNPs by atomic force microscopy indicated that the RNA is significantly bent or condensed in the complex.

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“…PARP-1 activity is also linked to coordination of chromatin structure and gene expression [103]. It was reported that PARP-1 can bind to DNA hairpins and promoter region in superhelical DNA and promote formation of cruciform structure [104]. PARP-1 recognizes distortions in the DNA backbone allowing it to interact with three- and four-way junctions [105].…”

Section: Proteins Involved In Interactions With Quadruplex Dnamentioning

confidence: 99%

“…Pull-down and chromatin immunoprecipitation assays revealed that this quadruplex-forming element is bound by MAZ and PARP-1 proteins [62]. It was also found that using plasmid DNA targets, binding of PARP-1 to DNA can induce changes in DNA topology [104]. Furthermore, a critical quadruplex-forming element of murine KRAS oncogene interacts with MAZ and PARP-1 proteins via conformational changes from duplex to quadruplex DNA.…”

Section: Proteins Involved In Interactions With Quadruplex Dnamentioning

confidence: 99%

DNA and RNA Quadruplex-Binding Proteins

Brázda

Hároníková

Liao

et al. 2014

IJMS

225

195

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Four-stranded DNA structures were structurally characterized in vitro by NMR, X-ray and Circular Dichroism spectroscopy in detail. Among the different types of quadruplexes (i-Motifs, minor groove quadruplexes, G-quadruplexes, etc.), the best described are G-quadruplexes which are featured by Hoogsteen base-paring. Sequences with the potential to form quadruplexes are widely present in genome of all organisms. They are found often in repetitive sequences such as telomeric ones, and also in promoter regions and 5' non-coding sequences. Recently, many proteins with binding affinity to G-quadruplexes have been identified. One of the initially portrayed G-rich regions, the human telomeric sequence (TTAGGG)n, is recognized by many proteins which can modulate telomerase activity. Sequences with the potential to form G-quadruplexes are often located in promoter regions of various oncogenes. The NHE III1 region of the c-MYC promoter has been shown to interact with nucleolin protein as well as other G-quadruplex-binding proteins. A number of G-rich sequences are also present in promoter region of estrogen receptor alpha. In addition to DNA quadruplexes, RNA quadruplexes, which are critical in translational regulation, have also been predicted and observed. For example, the RNA quadruplex formation in telomere-repeat-containing RNA is involved in interaction with TRF2 (telomere repeat binding factor 2) and plays key role in telomere regulation. All these fundamental examples suggest the importance of quadruplex structures in cell processes and their understanding may provide better insight into aging and disease development.

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DNA transitions induced by binding of PARP‐1 to cruciform structures in supercoiled plasmids

Cited by 38 publications

References 38 publications

The KRAS Promoter Responds to Myc-associated Zinc Finger and Poly(ADP-ribose) Polymerase 1 Proteins, Which Recognize a Critical Quadruplex-forming GA-element

The KRAS Promoter Responds to Myc-associated Zinc Finger and Poly(ADP-ribose) Polymerase 1 Proteins, Which Recognize a Critical Quadruplex-forming GA-element

Hepatitis Delta Antigen Requires a Flexible Quasi-Double-Stranded RNA Structure To Bind and Condense Hepatitis Delta Virus RNA in a Ribonucleoprotein Complex

DNA and RNA Quadruplex-Binding Proteins

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