Natural Occurrence of Left-Handed (Z) Regions in PM2 DNA

Miller, Fletcher; Jorgenson, K. F.; Winkfein, Robert J.; Sande, J.H. van de; Zarling, David A.; Stockton, John F.; Rattner, J. B.

doi:10.1080/07391102.1983.10507468

Cited by 18 publications

(5 citation statements)

References 27 publications

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“…Segments of Z-DNA also appear to exist in native genomes such as the interband region of the Drumphila polytene chromosome (9) and bacteriophage PM2 (33). It is further reported that DNA isolarted from a few selected SLE patients contains a higher percentage of G-C than that found in normal controls (15,16).…”

Section: Discussionmentioning

confidence: 99%

Effects of lupus‐inducing drugs on the B to Z transition of synthetic DNA

Thomas

Messner

1986

Arthritis & Rheumatism

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Five drugs associated with systemic lupus erythematosus were studied for their effect on the salt-induced right-handed (B) to left-handed (Z) transition of poly (dG-me5dC) . poly(dG-me5dC). Using circular dichroism spectroscopy, procainamide and hydralazine were found to reduce the midpoint of B to Z transition from 0.8M NaCl to 0.5M NaCl and to increase the rate of this transition at 1M NaCI. Isoniazid and D-penicillamine had less effect on the midpoint of transition and practically no effect on the kinetics. N-acetyl procainamide (a structurally related control for procainamide) and L-canavanine had no effect. Procainamide caused slight reduction in the helix-coil transition (melting) temperature of calf thymus DNA. At a concentration of 1 : 1 (DNA phosphate : drug ratio), procainamide and hydralazine also caused the aggregation of calf thymus DNA. Since altered DNA conformations, such as Z-DNA, are more immunogenic, these results suggest that the induction or stabilization of Z-DNA by these drugs might be important in the pathogenesis of at least some cases of systemic lupus erythematosus.The presence of a variety of antibodies showing differing degrees of specificity to nuclear components-DNA, RNA, histones-is the hallmark of idio- pathic and drug-induced systemic lupus erythematosus (SLE) ( 1 4 ) . In addition to antibodies against right-handed (B) DNA and single-stranded (ss) DNA, recent reports indicate the presence of antibodies to left-handed (Z) DNA in SLE patient sera (5,6). Antibodies raised from the autoimmune MRL/lpr-lpr mouse strain also show specificity for different forms of Z-DNA (7). Z-DNA is an effective antigen, as demonstrated by Lafer et a1 (8), who produced anti-Z-DNA antibodies by exogenous administration of brominated poly(dG-dC) . poly(dG-dC) in mice and rabbits. Using these antibodies, the presence of segments of Z-DNA has been revealed in some native genomes, such a s the interband region of the Drosophila polytene chromosome (9).The DNA sequences which are capable of converting to the Z form in the presence of salts, alcohols, and polyamines are mainly constituted of alternating purine-pyrimidines: specifically, dG-dC and its derivatives (10). However, DNA sequences consisting of (dT-dG), . (dC-dA), also undergo the right-handed to left-handed transition upon covalent modification with drugs such as acetylaminofluorene (1 1). These potential Z-DNA-forming sequences are widely dispersed in the human genome (12) and other native DNAs (13). Van Helden (14) recently reported that DNA fragments isolated from the serum of an SLE patient were rich in these potentially Z-DNA-forming regions. Similarly , Sano and Morimoto (1 5,16) reported that DNA fragments isolated from DNA-anti-DNA immune complexes contained a higher percentage of guaninecytosine (G-C) sequences compared with the average percentage of such sequences in total human DNA (5040% versus 38%). In addition, SLE sera show a high binding affinity for DNA fragments containing elevated G-C content or Z-form conformation (17).

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Section: Discussionmentioning

confidence: 99%

Effects of lupus‐inducing drugs on the B to Z transition of synthetic DNA

Thomas

Messner

1986

Arthritis & Rheumatism

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“…The region surrounding the (AC)"-rich repeat in TP17 was also sequenced, and this led to the identification of several additional alternating purine-pyrimidine sequences downstream of the (AC)"-rich region. Our criteria for identifying such sequences are five (or more) uninterrupted alternating purine-pyrimidines or eight (or more) with a single interruption (Miller et al, 1983). Though several regions meet these criteria, most are small (less than 13 nucleotides in length).…”

Section: Resultsmentioning

confidence: 99%

Tandem repeats of a specific alternating purine-pyrimidine DNA sequence adjacent to protamine genes in the rainbow trout that can exist in the Z form

Aiken¹,

Miller²,

Hagen³

et al. 1985

Biochemistry

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We have located an extensive (AC)n-rich but specific sequence downstream of three rainbow trout protamine genes. Although sharing considerable sequence homology, including a perfectly conserved 46 base pair repeat, the sequences exhibit a regular heterogeneity in the length of the (AC)n-rich tracts. Radioimmunoassay experiments, S1 nuclease sensitivity studies, two-dimensional electrophoretic analysis, and immunoelectron microscopy studies have been used to determine if the region could assume a Z DNA conformation. It was found that, in a supercoiled plasmid, the (AC)n-rich region has the ability to attain the Z DNA conformation under physiological conditions.

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“…5). However, we note as a potential site the qAF at 3555 (which meets both definitions) and which is within the resolution limits of the site identified by e.m. Studies of the PM2 bacteriophage genome also provides evidence for the correspondence of anti Z-DNA Ig binding sites to tracts of purine-pyrimidine repetitions (24,25). The immunoelectron microscopy mapping of anti-Z-DNA Ig binding sites in the purine-pyrimidine rich region of this phage DNA (26) shows the existence of Z-DNA within a protein coding region.…”

mentioning

confidence: 89%

“…The mapping of anti-Z-DNA immunogLobuLin binding sites by immunoelectron microscopy provides severaL exampLes of naturally ocurring Z-DNA tracts in 0X174 (23), PM2 (24)(25)(26) and SV40 (18,27) DNAs. Corresponding data aLso exist for the cloning vector pBR322 (8).…”

Section: Introductionmentioning

confidence: 99%

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

Konopka¹,

Reiter

Jung

et al. 1985

Nucl Acids Res

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The recent electronmicroscopic and biochemical mapping of Z-DNA sites in phi X174, SV40, pBR322 and PM2 DNAs has been used to determine two sets of criteria for identification of potential Z-DNA sequences in natural DNA genomes. The prediction of potential Z-DNA tracts and corresponding statistical analysis of their occurrence have been made on a sample of 14 DNA genomes. Alternating purine and pyrimidine tracts longer than 5 base pairs in length and their clusters (quasi alternating fragments) in the 14 genomes studied are under-represented compared to the expectation from corresponding random sequences. The fragments [d(G X C)]n and [d(C X G)]n (n greater than or equal to 3) in general do not occur in circular DNA genomes and are under-represented in the linear DNAs of phages lambda and T7, whereas in linear genomes of adenoviruses they are strongly over-represented. With minor exceptions, potential Z-DNA sites are also under-represented compared to random sequences. In the 14 genomes studied, predicted Z-DNA tracts occur in non-coding as well as in protein coding regions. The predicted Z-DNA sites in phi X174, SV40, pBR322 and PM2 correspond well with those mapped experimentally. A complete listing together with a compact graphical representation of alternating purine-pyrimidine fragments and their Z-forming potential are presented.

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Natural Occurrence of Left-Handed (Z) Regions in PM2 DNA

Cited by 18 publications

References 27 publications

Effects of lupus‐inducing drugs on the B to Z transition of synthetic DNA

Effects of lupus‐inducing drugs on the B to Z transition of synthetic DNA

Tandem repeats of a specific alternating purine-pyrimidine DNA sequence adjacent to protamine genes in the rainbow trout that can exist in the Z form

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

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