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1 Z-DNA conformation in the d(CG)n sequences was assayed b
2 Z-DNA formation in the WC gene (c-myc) was affected diff
3 Z-DNA formation in this sequence was detected at the bas
4 Z-DNA forms sequence-specifically with a preference for
5 Z-DNA, the left-handed conformer of DNA, is stabilized b
6 Z-DNA-binding domains of other proteins are equally effe
7 Z-DNA-binding protein 1 (ZBP1) is an innate immune senso
8 Z-DNA-binding protein 1 (ZBP1), initially reported as an
9 Z-DNA-binding protein 1 (ZBP1; also known as DAI or DLM-
10 Z-DNA/RNA is recognised by Z-binding domains (ZBDs), whi
12 ith the crystal structure of the (Zalpha)(2)/Z-DNA complex shows that most Z-DNA contacting residues
13 tide-repeat sequence that is able to adopt a Z-DNA conformation both in vitro and in vivo and interac
14 e promoter region induced or stabilized by a Z-DNA-binding protein can act as a cis-element in gene r
20 igh-resolution non-disordered structure of a Z-DNA hexamer containing two AT base pairs in the interi
22 have hypothesized that the recognition of a Z-DNA sequence by the Zalpha(ADAR1) domain is context sp
24 we describe the effects of the presence of a Z-DNA-forming DNA sequence on the basal levels of expres
27 profound effect in conferring stability to a Z-DNA conformation via electrostatic complementarity and
28 ystem, the reporter gene is activated when a Z-DNA-specific binding domain is fused with an activatio
29 nce of Z-DNA was detected by cleavage with a Z-DNA specific nuclease, by undermethylation using Z-DNA
31 Supercoiled plasmids were incubated with a Z-DNA-specific antibody (Z22) and passed over a protein
32 cal library values with the present accurate Z-DNA parameters, shows in general a good agreement, but
33 iched between the blunt-ends of two adjacent Z-DNA duplexes, while the overhanging base of the opposi
34 moters, or regions with the ability to adopt Z-DNA conformation, have been hypothesized to enhance re
36 NA decamer d(GCACGCGTGC) and the alternating Z-DNA decamer d(GCGCGCGCGC) and discussed in terms of th
37 observed that methylation of the alternating Z-DNA oligomer d(GCGCGCGCGC), which starts with a 5'-pur
41 or competitive spermine binding to B-DNA and Z-DNA, we can make predictions for how potential Z-DNA s
46 adapter-inducing interferon-beta (TRIF) and Z-DNA-binding protein 1 (ZBP1)/DNA-dependent activator o
49 lated VH domain of immunization-induced anti-Z-DNA Ab resembles the activity of natural autoantibodie
58 ending, stretching, and torsional behaviors; Z-DNA to be at least three-fold stiffer than random-sequ
59 ls depends on the virus-encoded bifunctional Z-DNA/double-stranded RNA (dsRNA)-binding protein E3.
62 orating a related protein that does not bind Z-DNA is not pathogenic, but a mutation that creates Z-D
63 larity to the Zalpha motif but does not bind Z-DNA, and with a mutant of hZbeta(ADAR1), which binds Z
65 ues in free Zalpha are prepositioned to bind Z-DNA, thus minimizing the entropic cost of binding.
66 rminal domain depends on its ability to bind Z-DNA; Z-DNA-binding domains from unrelated mammalian pr
68 f mAb Z22 and that the VH domain alone binds Z-DNA with an affinity similar to that of whole variable
71 romosome 22 genomic sequence shows that both Z-DNA forming regions (ZDRs) and promoter sites for nucl
73 the extent of transcriptional enhancement by Z-DNA is promoter-specific and determined by its separat
75 as been replaced in Zab with Zalpha, cleaves Z-DNA regions in supercoiled plasmids more efficiently t
78 onally regulated by a mechanism that couples Z-DNA with NFI activation, similar to the mechanism prev
80 ce-dependent structures, such as cruciforms, Z-DNA, or H-DNA, even though they are not favored by con
81 triplexes, quadruplexes, hairpin/cruciforms, Z-DNA and single-stranded looped-out structures with imp
83 ide steps, traditionally thought to disfavor Z-DNA, can be incorporated within heterogeneous Z-DNA co
84 sm by demonstrating the ability of a distant Z-DNA-forming site to compete with the superhelical dest
86 domain depends on its ability to bind Z-DNA; Z-DNA-binding domains from unrelated mammalian proteins
87 g of Zab to potential as well as established Z-DNA segments suggests that the range of biological sub
89 t activator of interferon regulatory factors/Z-DNA binding protein 1 (DAI/ZBP1) bound plasmid DNA in
93 eavy chain CDR3 amino acids are critical for Z-DNA binding by the single chain variable fragment (scF
95 acterizing sequence-specific preferences for Z-DNA formation and B-Z junction localization within het
97 repair complex, Msh2-Msh3, are required for Z-DNA-induced genetic instability in yeast and human cel
98 ne-hybrid assay, we compared the results for Z-DNA binding of vZ(E3L) with those for human Zbeta(ADAR
100 g tandem GT repeats, which are known to form Z-DNA and interact with several components of the recomb
103 g pyrimidine-purine sequences typically form Z-DNA, with the pyrimidines in the anti and purines in t
104 tory effect on T7 transcription results from Z-DNA formation in the (CG)(14) sequence rather than fro
108 ows apparent specificity for the left-handed Z-DNA conformation adopted by alternating (dGdC) polymer
110 Since its discovery in 1979, left-handed Z-DNA has evolved from an in vitro curiosity to a challe
112 n, (ii) the self-organization of left-handed Z-DNA with alternating [dC-dG] sequences in the solid st
118 pha, which is sufficient to bind left-handed Z-DNA; however, the substrate binding is strikingly diff
121 NA, can be incorporated within heterogeneous Z-DNA containing B-Z junctions upon binding to the Zalph
124 structures form six base-pairs of identical Z-DNA duplexes with single nucleotides overhanging at th
128 contribute to GC-rich sequences occurring in Z DNA with a higher frequency than AT-rich sequences.
132 that mutation of key amino acids involved in Z-DNA/RNA binding in ZBP1's ZBDs prevented necroptosis u
134 A structure predictions available, including Z-DNA motifs, quadruplex-forming motifs, inverted repeat
139 cate that the incorporation of CC steps into Z-DNA is driven by favorable sequence-specific Z-Z and B
140 od, starting with d(pGpC) of the isomorphous Z-DNA hexamer d(araC-dG)3 without the 2'-OH group of ara
141 es focusing on the ADAR p150 isoform and its Z-DNA- and Z-RNA-specific Zalpha domain find support fro
142 some teleost species another protein kinase, Z-DNA-dependent protein kinase (PKZ), plays a similar ro
146 he (Zalpha)(2)/Z-DNA complex shows that most Z-DNA contacting residues in free Zalpha are preposition
152 virus has sequence similarity to a family of Z-DNA binding proteins of defined three-dimensional stru
153 )), which is similar to the Zalpha family of Z-DNA-binding proteins, are required for infection.
154 deling enzyme, BRG1, results in formation of Z-DNA at the TG repeat sequence located within the promo
155 ription is not required for the formation of Z-DNA but does result in an expanded region of Z-DNA.
156 rmeabilized nuclei to study the formation of Z-DNA in this sequence at various levels of transcriptio
158 -hybrid system is made in which formation of Z-DNA is studied near a minimal promoter site where it c
159 d structural changes, including formation of Z-DNA, play an important role in the catalytic function
162 that NHEJ plays a role in the generation of Z-DNA-induced large-scale deletions, suggesting that thi
163 e more compact three-dimensional geometry of Z-DNA, both water and salt are found to strongly stabili
168 ymerase during transcription, recognition of Z-DNA by DRADA1 provides a plausible mechanism by which
169 functional data suggest that recognition of Z-DNA by Zalpha involves residues in both the alpha3 hel
172 t may specifically direct protein regions of Z-DNA induced by negative supercoiling in actively trans
182 ZIP also has potential for engineering other Z-DNA specific proteins for future studies of Z-DNA in v
183 nally show that the Zalpha domain from other Z-DNA-binding proteins (ZBP1, E3L) is likewise sufficien
186 factor I (NFI) binding sites, and potential Z-DNA forming regions (ZDRs) as representative structura
187 A, we can make predictions for how potential Z-DNA sequences found in the human genome are affected b
188 which these complexes recognize and process Z-DNA in eukaryotes, representing a mechanism of Z-DNA-i
189 results reveal that mammalian cells process Z-DNA-forming sequences in a strikingly different fashio
190 se a model in which the BAF complex promotes Z-DNA formation which, in turn, stabilizes the open chro
192 mulatory effect exerted by promoter proximal Z-DNA is not affected by helical phasing relative to the
193 element, by interacting with these putative Z-DNA-binding proteins, is involved in the maintenance o
196 itutions that eliminated or markedly reduced Z-DNA binding by scFv instead caused a modest increase o
198 iation with a highly polymorphic regulatory, Z-DNA-forming microsatellite of (GT/AC)n dinucleotides w
200 the activation of the CSF1 promoter requires Z-DNA-forming sequences that are converted to Z-DNA stru
201 , circular dichroism (CD) study has revealed Z-DNA formation with the monovalent metal ions, Zn(2+) a
204 ther, we identified the innate immune sensor Z-DNA binding protein 1 (ZBP1) as the apical sensor of f
205 tic repulsions among the more closely spaced Z-DNA phosphates destabilize this form compared to B-DNA
207 umes a left-handed double helical structure (Z-DNA), whereas the unmethylated (dC-dG)(4) analog remai
211 e deaminase (ADAR1), contains two N-terminal Z-DNA-binding motifs, Zalpha and Zbeta, the function of
212 more, our results reveal that the N-terminal Z-DNA/RNA binding domain of vaccinia virulence factor E3
214 data presented in this report establish that Z-DNA formation is an important mechanism in modulating
216 rovides additional support to the model that Z-DNA binding proteins may regulate biological processes
219 hin heterogeneous sequences and suggest that Z-DNA can in principle propagate into a wider range of g
222 ng relative to the TATA box, suggesting that Z-DNA effects transcription without interacting with the
225 serine with threonine at residue 186 in the Z DNA-binding domain differentially affects its ability
226 We now report that serine residue 186 in the Z DNA-binding domain plays an important role in the abil
229 Formation of sequences by both BRG1 and the Z-DNA is required for effective chromatin remodeling of
231 i-polymerlike structure that has assumed the Z-DNA conformation further strengthened by the long inne
234 ence of the flanking sequence containing the Z-DNA-forming tract reduced the extent of slipped-strand
236 RNA binding domain and a region covering the Z-DNA binding domain and the nuclear export signal compr
237 by transcription, as recently shown for the Z-DNA forming sequence (CG)(14), which causes genomic in
239 ults expose higher-order complexities in the Z-DNA code within heterogeneous sequences and suggest th
243 different DSB repair pathways influenced the Z-DNA-induced mutagenesis, we engineered bacterial E.col
244 -)dependent DNA strand-breaks occur near the Z-DNA-forming region in human cell extracts, and we mode
245 (M246), which retains the second half of the Z-DNA binding domain, all RNA binding domains, and the d
248 rivative, up to 4,000-fold enrichment of the Z-DNA-containing plasmid was demonstrated per cycle of t
250 he putative nuclear localization signal, the Z-DNA binding domain, and the entire RNA binding domain
255 assayed by (i) a band shift assay using the Z-DNA-specific Z22 monoclonal antibody (ZIBS assay); (ii
256 ults reported here support a model where the Z-DNA binding motifs target ADAR1 to regions of negative
257 5 M Na+ is significantly perturbed while the Z-DNA domain is less perturbed by the presence of the mi
259 sting that Z alpha nuclease binds within the Z-DNA insert, but cleaves in the nearby B-DNA, by using
261 umors is likely due to a marked loss of this Z-DNA-mediated transcriptional suppression function.
263 the Zalpha motif binds with high affinity to Z-DNA as a dimer, that the binding site is no larger tha
265 effected by the superhelically induced B- to Z-DNA transition in a manner that is both orientation an
270 conformation in poly(dG-d5meC) and binds to Z-DNA stabilized by bromination with high affinity and s
272 -DNA-forming sequences that are converted to Z-DNA structure upon activation by the BAF complex.
273 d from E. coli, the transition from B-DNA to Z-DNA occurred from d(CG)4, to d(CG)5, with 20% of d(CG)
277 nating purine/pyrimidines, which is prone to Z-DNA transition, is much stronger than to other types o
279 that the Zalpha(ADAR1) binds specifically to Z-DNA and preferentially to d(CG)(n) inserts, which requ
284 y in vertebrates and is characterized by two Z-DNA-binding motifs, the biological function of which r
285 ded RNA adenosine deaminase, type 1) has two Z-DNA binding motifs, Zalpha and Zbeta, the function of
286 monstrated that T-T and A-A bases in the two Z-DNA duplexes are dynamic and adopt a range of conforma
287 specific nuclease, by undermethylation using Z-DNA sensitive SssI methylase, and by circular dichrois
294 he plasmids using fusion nucleases, in which Z-DNA-binding peptides from the N terminus of double-str
295 a new epigenetic regulatory process in which Z-DNA/MeCP2/NF1 interaction leads to transcriptional sup
296 ncluding a crystal structure in complex with Z-DNA, have focused on the human ADAR1 Zalpha domain in
298 Zalpha and map the interaction surface with Z-DNA, confirming roles previously assigned to residues
299 r p150 WT isoform or the p150 Zalpha (Y177A) Z-DNA-binding mutant of ADAR1 restored suppression of ho
300 ts the RHIM-containing adaptor protein ZBP1 (Z-DNA binding protein 1; also known as DAI or DLM1) from