Concordance of experimentally mapped or predicted Z-DNA sites with positions of selected alternating purine-pyrimidine tracts

Konopka, Andrzej K.; Reiter, Johanes; Jung, Manfred; Zarling, David A.; Jovin, Thomas M.

doi:10.1093/nar/13.5.1683

Cited by 28 publications

(17 citation statements)

References 26 publications

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“…However, the SV40 genome contains few d(G-C)n sequences and as a consequence, our binding data do not permit an assessment of the minimum length requirement for such regions in the Z conformation. This point is discussed further in Revet et al (1984), in Miller et al (in preparation; this study deals with the plasmid pBR322 DNA and phage PM-2 DNA as substrates for anti-Z IgG), and in Konopka et al (1985; a general survey of numerous viral and episomal sequences).…”

Section: Sv40 Sequences Binding Anti-z Iggmentioning

confidence: 88%

Electron microscopy of SV40 DNA cross-linked by anti-Z DNA IgG.

Hagen¹,

Zarling²,

Jovin

1985

The EMBO Journal

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Electron microscopy has revealed the specific binding of bivalent anti-Z DNA immunoglobulin G (IgG) to different sites on supercoiled Form I SV40 DNA. The anti-Z IgG links together left-handed regions located within individual or on multiple SV40 DNA molecules at the superhelix density obtained upon extraction. Velocity sedimentation, electrophoresis, and electron microscopy all show that two or more Z DNA sites in the SV40 genome can be intermolecularly cross-linked with bivalent IgG into high mol. wt. complexes. The formation and stability of the intermolecular antibody-DNA complexes are dependent on DNA superhelix density, as judged by three criteria: (1) relaxed circular (Form II) DNA does not react; (2) release of torsional stress by intercalation of 0.25 itM ethidium bromide removes the antibody; and (3) linearization with specific restriction endonucleases reverses antibody binding and DNA cross-linking. Nonimmune IgG does not bind to negatively supercoiled SV40 Form I DNA, nor are complexes observed in the presence of competitive synthetic polynucleotides constitutively in the left-handed Z conformation; B DNA has no effect. Using various restriction endonucleases, three major sites of anti-Z IgG binding have been mapped by electron microscopy to the 300-bp region containing nucleotide sequences controlling SV40 gene expression. A limited number of minor sites may also exist (at the extracted superhelix density). Key words: left-handed Z DNA/enhancer/alternating purine-pyrimidine Introduction We have previously developed an electrophoretic assay which detected left-handed Z DNA sites in SV40 DNA (and other circular genomes) using anti-Z DNA IgG binding to negatively supercoiled Form I molecules (Zarling et al., 1984a(Zarling et al., , 1984b. The formation of DNA-IgG complexes depended on external conditions (ionic strength and temperature), nucleotide sequence, the physical state of the DNA (torsional stress) and the anti-DNA immunoglobulin (specificity, valency and concentration). Changes in electrophoretic migration were attributed to the formation of various oligomeric species; the existence of trimers suggested the expression of at least two Z DNA sites per SV40 DNA.In the present study, SV40 Form I DNA-IgG complexes-were preparatively purified by velocity sedimentation using conditions which optimally stabilize natural Z DNA sequences in protein-

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Section: Sv40 Sequences Binding Anti-z Iggmentioning

confidence: 88%

Electron microscopy of SV40 DNA cross-linked by anti-Z DNA IgG.

Hagen¹,

Zarling²,

Jovin

1985

The EMBO Journal

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“…The first method, developed by the Jovin group, seeks to identify Z-susceptible sites based solely on their sequence characteristics [46]. The energetics of transition were not considered in this approach.…”

Section: Introductionmentioning

confidence: 99%

Theoretical Analysis of the Stress Induced B-Z Transition in Superhelical DNA

Zhabinskaya

Benham

2011

PLoS Comput Biol

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We present a method to calculate the propensities of regions within a DNA molecule to transition from B-form to Z-form under negative superhelical stresses. We use statistical mechanics to analyze the competition that occurs among all susceptible Z-forming regions at thermodynamic equilibrium in a superhelically stressed DNA of specified sequence. This method, which we call SIBZ, is similar to the SIDD algorithm that was previously developed to analyze superhelical duplex destabilization. A state of the system is determined by assigning to each base pair either the B- or the Z-conformation, accounting for the dinucleotide repeat unit of Z-DNA. The free energy of a state is comprised of the nucleation energy, the sequence-dependent B-Z transition energy, and the energy associated with the residual superhelicity remaining after the change of twist due to transition. Using this information, SIBZ calculates the equilibrium B-Z transition probability of each base pair in the sequence. This can be done at any physiologically reasonable level of negative superhelicity. We use SIBZ to analyze a variety of representative genomic DNA sequences. We show that the dominant Z-DNA forming regions in a sequence can compete in highly complex ways as the superhelicity level changes. Despite having no tunable parameters, the predictions of SIBZ agree precisely with experimental results, both for the onset of transition in plasmids containing introduced Z-forming sequences and for the locations of Z-forming regions in genomic sequences. We calculate the transition profiles of 5 kb regions taken from each of 12,841 mouse genes and centered on the transcription start site (TSS). We find a substantial increase in the frequency of Z-forming regions immediately upstream from the TSS. The approach developed here has the potential to illuminate the occurrence of Z-form regions in vivo, and the possible roles this transition may play in biological processes.

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“…not significant). G/C-rich tracts of 9 to 30 guanines or cytosines [13]; PUPY: purine/pyrimidine tracts of 5 to 25 alternating purines and pyrimidines [14]; OLIGOPU: tracts of 15 to 25 purines [15,16]; TOPO II:…”

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confidence: 99%

Chromosome translocations in cancer: computational evidence for the random generation of double-strand breaks

Novo

Vizmanos

2006

Trends in Genetics

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We show that introns harboring translocation breakpoints in tumors are significantly longer than non-translocated introns of the same genes, but are not significantly enriched in sequence elements potentially involved in chromosomal rearrangements. Our findings provide evidence that double-strand breaks, the type of DNA damage that leads to translocations in tumors, are created at random in the genome, and that sequence elements do not play a general role in the localization of the breaks. Translocation breakpoints in cancerChromosome aberrations are a common feature of cancer initiation and progression. Several types of aberrations are found in tumors, reciprocal translocations being one of the best characterized types of genetic alteration found in known cancer genes [1]. It is widely accepted that chromosome rearrangements in cancer are mediated by the repair of DNA double-strand breaks (DSB) through non-homologous end joining (NHEJ), which seems to be the major repair pathway in human somatic cells [2][3][4].Analysis of some translocations, especially in hematological malignancies, revealed that the breakpoints are some times distributed in a non-random fashion, either densely clustered in particular regions of some genes, or more diffusely clustered along one or a few specific introns in other genes [5]. This has led to suggestions that the presence of local chromatin features or specific sequence motifs can determine genomic domains that are particularly prone to sustain a DSB in the vicinity. In line with this view, various sequence elements have been reported to be associated with chromosomal rearrangements in tumors (reviewed in [6]). However, since clustering of breakpoints is not observed in most translocations identified to date, there is considerable debate as to whether the presence of DNA domains with a high risk of sustaining a DSB is important only in a few specific translocations, or it is a general feature common to all translocations in human tumors. The lack of a significant number of breakpoints cloned at the genomic level has delayed progress in this area, because the precise localization of the breakpoints and the sequence surrounding them is known only in a limited number of cases. 2In order to address this issue we have performed computational studies that enabled us to precisely locate a large number of cancer translocation breakpoints on the human genome reference sequence, and to analyze the genes involved with a view to unveil any potential factors accounting for the localization of breakpoints in human tumors. Features of the genes involved in reciprocal translocations in tumorsWe collected 268 genes whose involvement in reciprocal translocations in various types of tumors has been reported in the literature, and extracted their sequence and annotations from the Ensembl database [7] using perl scripts and the Application Programming Interface (API) provided by the Ensembl project [8]. We compared various sequence features between these genes and a group of 9,406 genes tha...

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Concordance of experimentally mapped or predicted Z-DNA sites with positions of selected alternating purine-pyrimidine tracts

Cited by 28 publications

References 26 publications

Electron microscopy of SV40 DNA cross-linked by anti-Z DNA IgG.

Electron microscopy of SV40 DNA cross-linked by anti-Z DNA IgG.

Theoretical Analysis of the Stress Induced B-Z Transition in Superhelical DNA

Chromosome translocations in cancer: computational evidence for the random generation of double-strand breaks

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