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1.
Kaluzhny D Laufman O Timofeev E Borisova O Manor H Shchyolkina A 《Journal of biomolecular structure & dynamics》2005,23(3):257-265
Translin is a human single-stranded DNA and RNA binding protein that has been highly conserved in eukaryotic evolution. It consists of eight subunits having a highly helical secondary structure that assemble into a ring. The DNA and the RNA are bound inside the ring. Recently, some of us demonstrated that the human translin specifically binds the single-stranded microsatellite repeats, d(GT)(n), the human telomeric repeats, d(TTAGGG)(n), and the Tetrahymena telomeric repeats, d(GGGGTT)(n). These data suggested that translin might be involved in recombination at d(GT)(n).d(AC)(n) microsatellites and in telomere metabolism. Other data indicated that translin might stimulate binding of telomerase to single-stranded telomeric overhangs by unwinding secondary structures formed by the telomeric repeats. Here we present a circular dichroism (CD) analysis of complexes formed between the human translin and the microsatellite and telomeric oligodeoxynucleotides d(GT)(12) and d(TTAGGG)(5). We report that conformational changes occur in both the translin and the oligodeoxynucleotides upon formation of the complexes. In translin octamers bound to the oligodeoxynucleotide d(GT)(12), the fraction of alpha-helices decreases from approximately 67% to approximately 50%, while the fraction of turns and of the unordered structure increases from approximately 11% to approximately 17% and from approximately 19% to approximately 24%, respectively. In the bound oligodeoxynucleotide d(GT)(12), we observed CD shifts which are consistent with a decrease of base stacking and a putative anti-syn switch of some guanines. The oligodeoxynucleotide d(TTAGGG)(5) formed intramolecular quadruplexes under the conditions of our assays and translin was found to unfold the quadruplexes into structures consisting of a single hairpin and three unwound single-stranded d(TTAGGG) repeats. We suggest that such unfolding could account for the stimulation of telomerase activity by translin mentioned above. 相似文献
2.
We have previously identified in human fibroblasts a multisubunit protein (designated PGB) that specifically bound single-stranded G-rich microsatellite DNA sequences. PGB was later found to be identical, or closely related to translin, an octameric protein that bound single-stranded DNA consisting of sequences flanking chromosomal translocations. Here, we report that recombinant translin binds single-stranded microsatellite repeats, d(GT)n, and G-strand telomeric repeats, d(TTAGGG)n, with higher affinities (Kdis approximately = 2 nM and Kdis approximately = 12.5 nM, respectively, in 100 mM NaCl and 25 degrees C) than the affinity with which it binds a prototypical sequence flanking translocation sites (Kdis approximately = 23 nM). Translin also binds d(GT)n and d(TTAGGG)n overhangs linked to double-stranded DNA with equilibrium constants in the nanomolar range. Formation of DNA quadruplexes by the d(TTAGGG)n repeats inhibits their binding to translin. A further study of the binding parameters revealed that the minimal length of d(GT)n and d(TTAGGG)n oligonucleotides that a translin octamer can bind is 11 nucleotides, but that such oligonucleotides containing up to 30 nucleotides can bind only a single translin octamer. However, the oligonucleotides d(GT)27 and d(TTAGGG)9 bind two octamers with negative cooperativity. Translin does not detectably bind single-stranded d(GT)n sequences embedded within double-stranded DNA. Based on our data, we propose that translin might be involved in the control of recombination at d(GT)n.d(AC)n microsatellites and in telomere maintenance. 相似文献
3.
Yu. V. Dutikova O. F. Borisova A. K. Shchyolkina J. Lin S. Huang A. A. Shtil D. N. Kaluzhny 《Molecular Biology》2010,44(5):823-831
5,10,15,20-Tetra-(N-methyl-3-pyridyl)porphyrin (TMPyP3) is a DNA-binding derivative of porphyrins. A comparative study of
the binding of this ligand to biologically significant DNA structures was performed. For this purpose, the interactions of
TMPyP3 with the antiparallel telomeric G-quadruplex d(TTAGGG)4, oligonucleotide dTTAGGGTTAGAG(TTAGGG)2 (not forming a quadruplex structure), double-stranded d(AC)8 · d(GT)8, and single-stranded d(AC)8 and d(GT)8 DNA molecules have been studied. Analysis of absorption isotherms has demonstrated that the binding constants and the number
of binding sites for the complexes TMPyP3: DNA increase in the following order: d(AC)8 < d(GT)8 < d(AC)8 · d(GT)8 = d(TTAGGG)4 < dTTAGGGTTAGAG(TTAGGG)2. It has been for the first time demonstrated that the constant for TMPyP3 binding to unfolded dTTAGGGTTAGAG(TTAGGG)2 strand (1.3 × 107 M−1) is approximately threefold higher than for the G-quadruplex d(TTAGGG)4 (4.7 × 106 M−1). Binding of two TMPyP3 molecules to d(TTAGGG)4 decreases the thermostability of G-quadruplex (ΔTm = −8°C). Circular dichroism spectra of the TMPyP3 complexes with d(TTAGGG)4 suggest that the ligand partially unfolds the G-quadruplex structure. Structural destabilization of the telomeric G-quadruplex
by TMPyP3 can explain the relatively low activity of this ligand as a telomerase inhibitor and a low cytotoxicity for cultured
tumor cells. 相似文献
4.
Bernhard Weber L. Allen R. Ellen Magenis P. J. Goodfellow L. Smith Michael R. Hayden 《Mammalian genome》1991,1(4):211-216
Eukaryotic telomeres are specialized DNA-protein structures that are thought to ensure chromosomal stability and complete replication of the chromosome ends. All telomeres which have been studied consist of a tandem array of G-rich repeats which seem to be sufficient for telomere function. Originally, the human telomeric repeat (TTAGGG)n was assumed to be exclusively located at the very end of all human chromosomes. More recent evidence, however, suggests an extension into proterminal regions. Very little is known about the interstitial distribution of telomeric repeats. Here we present evidence for the presence of (TTAGGG)n repeats in internal loci on the long and short arms of different human chromosomes. In addition, we studied the genomic organization of these repeats in more detail and discuss possible functions of interstitial telomeric repeats in the human genome. 相似文献
5.
Dutikova IuV Borisova OF Shchelkina AK Lin J Huang S Shtil' AA Kaliuzhnyĭ DN 《Molekuliarnaia biologiia》2010,44(5):929-937
We studied the parameters of binding of 5,10,15,20-tetra-(N-methyl-3-pyridyl)porphyrin (TMPyP3) to the anti-parallel human telomeric G-quadruplex d(TTAGGG)4, the oligonucleotide dTTAGGGTTAGAG(TTAGGG)2 that does not form a quadruplex structure, as well as to the double stranded d(AC)8 x d(GT) and single stranded d(AC)8 and d(GT)8 DNAs. The analysis of absorption revealed that the binding constants and the number of DNA binding sites for TMPyP3 were d(AC)8 < d(GT)8 < d(AC)8 x d(GT)8 = d(TTAGGG)4 < dTTAGGGTTAGAG(TTAGGG)2. We demonstrated for the first time that the binding constant of TMPyP3 with the non-quadruplex chain dTTAGGGTTAGAG(TTAGGG)2 (1.3 x 10(7) M(-1)) is approximately 3 times bigger than the binding constant with the quadruplex d(TTAGGG)4 (4.6 x 10(6) M(-1)). Binding of two TMPyP3 molecules to d(TTAGGG)4 led to a decrease of thermostability of the G-quadruplex (deltaT(m) = -8 degrees C). Circular dichroism spectra of TMPyP3:d(TTAGGG)4 complexes revealed a shift of DNA structure from the G-quadruplex to an irregular chain. We hypothesize that partial destabilization of the telomeric G-quadruplex by TMPyP3 might be a reason for relatively low potency of this ligand as a telomerase inhibitor, as well as its marginal cytotoxicity for cultured tumor cells. 相似文献
6.
Xiao-Yan Zhang En-Hua Cao Yan Zhang Chunqing Zhou Chunli Bai 《Journal of biomolecular structure & dynamics》2013,31(5):693-701
Abstracts The telomeric DNA oligomers, d(TTAGGG)n where n=1, 2, 4, could self-associate into the multi-stranded structures in appropriate condition and exhibited a different CD spectra. The present of Na+ was more advantage to facilitate the formation of anti-parallel conformation, but the present of K+ enhanced their thermal stability. Spectroscopic analysis of 3, 3′- diethyloxadicarbocyanine (DODC) showed the formation of hairpin quadruplex structures for d(TTAGGG)2 and d(TTAGGG)4, but d(TTAGGG) could not. The four-stranded tetraplexes and branched nanowire formed in the present of K+ or Na+ alone were observed by atomic force microscopy (AFM). The ability to self-assemble of d(TTAGGG)n into four-stranded tetraplexes and nanowires depends strongly on the number of repeating units and ionic environment. A model to explain how these structures formed is proposed. 相似文献
7.
Human telomeres are composed of duplex TTAGGG repeats and a 3' single-stranded DNA tail. The telomeric DNA is protected and regulated by the shelterin proteins, including the protection of telomeres 1 (POT1) protein that binds telomeric single-stranded DNA. The single-stranded tail can fold into G-quadruplex (G4) DNA. Both POT1 and G4 DNA play important roles in regulating telomere length homeostasis. To date, most studies have focused on individual quadruplexes formed by four TTAGGG repeats. Telomeric tails in human cells have on average six times as many repeats, and no structural studies have examined POT1 binding in competition with G4 DNA folding. Using single molecule atomic force microscopy imaging, we observed that the majority of the telomeric tails of 16 repeats formed two quadruplexes even though four were possible. The result that physiological telomeric tails rarely form the maximum potential number of G4 units provides a structural basis for the coexistence of G4 and POT1 on the same DNA molecule, which is observed directly in the captured atomic force microscopy images. We further observed that POT1 is significantly more effective in disrupting quadruplex DNA on long telomeric tails than an antisense oligonucleotide, indicating a novel POT1 activity beyond simply preventing quadruplex folding. 相似文献
8.
Summary Using a series of genetic parameters, attempts have been made for more than two decades to establish the close kinship of human (Homo sapiens) with chimpanzee (Pan troglodytes). Molecular and cytogenetic data presently suggest that the two species are closely related. The recent isolation of a human telomeric probe (P5097-B.5) has prompted us to cross hybridize it to chimpanzee chromosomes in order to explore convergence and/or divergence of the telomeric repeat sequences (TTAGGG)n. On hybridization, the human probe bound to both ends (telomeres) of chimpanzee chromosomes, suggesting a concerted evolution of tandemly repeated short simple sequences (TTAGGG)n. Even the terminal heterochromatin of chimpanzee chromosomes was found to be endowed with telomeric repeats, suggesting that evolution of heterochromatin and capping with tandemly repeated short sequences are highly complex phenomena. 相似文献
9.
Distinct domains in the CArG-box binding factor A destabilize tetraplex forms of the fragile X expanded sequence d(CGG)n 总被引:2,自引:0,他引:2
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Formation of hairpin or tetraplex structures of the FMR1 gene d(CGG)n sequence triggers its expansion, setting off fragile X syndrome. In searching for proteins that destabilize d(CGG)n secondary structures we purified from rat liver quadruplex telomeric DNA binding protein 42 (qTBP42) that disrupts G′2 bimolecular tetraplex d(CGG)n while paradoxically stabilizing the G′2 structure of the telomeric sequence d(TTAGGG)n. Based on peptide sequence homology of qTBP42 and mouse CArG-box binding factor A (CBF-A), we provide direct evidence that recombinant CBF-A protein is physically and immunochemically indistinguishable from qTBP42 and that it too destabilizes G′2 d(CGG)n while stabilizing G′2 d(TTAGGG)n. We inquired whether CBF-A employs the same or different domains to differentially interact with G′2 d(CGG)n and G′2 d(TTAGGG)n. Mutant CBF-A proteins that lack each or combinations of its five conserved motifs: RNP11, RNP12, RNP21, RNP22 and ATP/GTP-binding box were tested for their G′2 d(CGG)n destabilization and G′2 d(TTAGGG)n stabilization activities. We find that either RNP11 or the ATP/GTP motifs are necessary and sufficient for G′2 d(CGG)n destabilization whereas RNP21 suppresses destabilization by either one of these two motifs. Neither RNP11 nor the ATP/GTP motif are required for G′2 d(TTAGGG)n stabilization. Hence, CBF-A employs different domains to destabilize G′2 d(CGG)n or stabilize G′2 d(TTAGGG)n. 相似文献
10.
Aparna Bansal 《Journal of biomolecular structure & dynamics》2020,38(7):1975-1983
AbstractGuanine rich DNA sequences of regulatory genomic regions form secondary structures known as G-quadruplexes usually stabilized by tetrads of Hoogsteen hydrogen bonded guanines. The in vivo existence of G-quadruplexes ascertains their biological roles. Human telomeric repeats are the most studied G-rich sequences. The four repeat Giardia telomeric sequence (TAGGG)4 differs from its human counterpart (TTAGGG)4, by deletion of one T at the G-tract intervening site of each repeat. We show here that whilst the two repeat Giardia telomeric sequence (TAGGG)2 forms parallel and antiparallel quadruplexes with tetramolecular topology exclusively, the four repeat version (TAGGG)4 forms a tetramolecular (antiparallel) and unimolecular (parallel) quadruplexes in Na+. The tetramolecular (antiparallel) G-quadruplex formed by four repeats of Giardia telomeric sequence is stabilized by the additional Watson-Crick bonding between its intervening TA bases aligned in antiparallel fashion. Four stranded antiparallel quadruplex for four repeats of any telomeric sequence have not been characterized till date. We hypothesize that telomeric association in antiparallel fashion, (via G-overhangs to form tetramolecular quadruplex) could be a biologically relevant molecular event. Further, coexistence of Hoogsteen as well as Watson-Crick base pairing might give insight for recognition of conformationally diverse DNA structures by ligands. Communicated by Ramaswamy H. Sarma 相似文献
11.
Polypteridae (Cladistia) is a family of archaic fishes, confined to African freshwaters. On account of their primitiveness
in anatomical and morphological characters and mosaic relationships among lower Osteichthyans fishes, they constitute an important
subject for the study of evolution in vertebrates. Very little is known about the karyological structure of these species.
In this article, a cytogenetic analysis on twenty specimens of Polypterus senegalus (Cuvier, 1829) was performed using both classical and molecular techniques. Karyotype (2n = 36; FN = 72), chromosome location of telomeric sequences (TTAGGG)
n
, (GATA)7 repeats and ribosomal 5S and 18S rRNA genes were examined by using Ag-NOR, classical C-banding, CMA3 staining and FISH. Staining with Ag-NOR showed the presence of two GC rich NORs on the p arm of the chromosome pair no. 1.
CMA3 marked all centromerical and some (no. 1 and no. 14) telomeric regions. FISH with 5S rDNA marked the subtelomeric region
of the q arm of the chromosome pair no. 14. FISH with 18S rDNA marked the telomeric region of the p arm of the chromosome
pair no. 1, previously marked by Ag-NOR. (GATA)7 repeats marked the subtelomeric regions of all chromosome pairs, with the exclusion of the no. 1, 3 and 14. Hybridization
with telomeric probes (TTAGGG)
n
showed bright signals at the end of all chromosomes. After cloning, the 5SrDNA alignment revealed an organization of sequences
made up of two different classes of tandem arrays (5S type I and 5S type II) of different lengths. 相似文献
12.
This paper reports on a successful application of fluorescent in situhybridization (FISH) with three repetitive DNA probes (ribosomal DNA (rDNA), (GATA)nand (TTAGGG)n) in the chromosomes of Fasciolaria lignaria(Mollusca: Prosobranchia: Neogastropoda). rDNA FISH consistently identified four chromosome pairs per spread in the three
examined specimens. The telomeric sequence (TTAGGG)nhybridized with termini of all chromosomes. GATA FISH revealed abundant, dispersed minisatellite regions which were not associated
to the XY sex-determining mechanism as indicated by the absence of a Y specific pattern of labelling.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
13.
Two congeneric mullet species, Mugil liza and M. curema, respectively with an all-uniarmed and an all-biarmed karyotype, were cytogenetically studied by base-specific fluorochrome staining and FISH-mapping of 45S and 5S ribosomal RNA genes (rDNA) and the (TTAGGG)n telomeric repeats. Whereas 45S rDNA sites might be homeologus in the two species, 5S rDNA sites are not, as they are localized on chromosome arms of different size. In both species, the (TTAGGG)n telomeric probe hybridized to natural telomeres and was found scattered along the NORs. In metacentric chromosomes of M. curema, no pericentromeric signals of the telomeric probe were detected. Data are discussed in relation to the karyotype evolution in Mugilidae and to the mechanisms and the evolutionary implications of Robertsonian rearrangements in M. curema. 相似文献
14.
Rama Rao Damerla Kelly E. Knickelbein Devin Kepchia Abbe Jackson Bruce A. Armitage Kristin A. Eckert Patricia L. Opresko 《DNA Repair》2010,9(11):1119-1129
Telomeres consisting of tandem guanine-rich repeats can form secondary DNA structures called G-quadruplexes that represent potential targets for DNA repair enzymes. While G-quadruplexes interfere with DNA synthesis in vitro, the impact of G-quadruplex formation on telomeric repeat replication in human cells is not clear. We investigated the mutagenicity of telomeric repeats as a function of G-quadruplex folding opportunity and thermal stability using a shuttle vector mutagenesis assay. Since single-stranded DNA during lagging strand replication increases the opportunity for G-quadruplex folding, we tested vectors with G-rich sequences on the lagging versus the leading strand. Contrary to our prediction, vectors containing human [TTAGGG]10 repeats with a G-rich lagging strand were significantly less mutagenic than vectors with a G-rich leading strand, after replication in normal human cells. We show by UV melting experiments that G-quadruplexes from ciliates [TTGGGG]4 and [TTTTGGGG]4 are thermally more stable compared to human [TTAGGG]4. Consistent with this, replication of vectors with ciliate [TTGGGG]10 repeats yielded a 3-fold higher mutant rate compared to the human [TTAGGG]10 vectors. Furthermore, we observed significantly more mutagenic events in the ciliate repeats compared to the human repeats. Our data demonstrate that increased G-quadruplex opportunity (repeat orientation) in human telomeric repeats decreased mutagenicity, while increased thermal stability of telomeric G-quadruplexes was associated with increased mutagenicity. 相似文献
15.
Human telomeres that contain (CTAGGG)n repeats show replication dependent instability in somatic cells and the male germline
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Aaron Mendez-Bermudez Mark Hills Hilda A. Pickett Anh Tuan Phan Jean-Louis Mergny Jean-Fran?ois Riou Nicola J. Royle 《Nucleic acids research》2009,37(18):6225-6238
A number of different processes that impact on telomere length dynamics have been identified but factors that affect the turnover of repeats located proximally within the telomeric DNA are poorly defined. We have identified a particular repeat type (CTAGGG) that is associated with an extraordinarily high mutation rate (20% per gamete) in the male germline. The mutation rate is affected by the length and sequence homogeneity of the (CTAGGG)n array. This level of instability was not seen with other sequence-variant repeats, including the TCAGGG repeat type that has the same composition. Telomeres carrying a (CTAGGG)n array are also highly unstable in somatic cells with the mutation process resulting in small gains or losses of repeats that also occasionally result in the deletion of the whole (CTAGGG)n array. These sequences are prone to quadruplex formation in vitro but adopt a different topology from (TTAGGG)n (see accompanying article). Interestingly, short (CTAGGG)2 oligonucleotides induce a DNA damage response (γH2AX foci) as efficiently as (TTAGGG)2 oligos in normal fibroblast cells, suggesting they recruit POT1 from the telomere. Moreover, in vitro assays show that (CTAGGG)n repeats bind POT1 more efficiently than (TTAGGG)n or (TCAGGG)n. We estimate that 7% of human telomeres contain (CTAGGG)n repeats and when present, they create additional problems that probably arise during telomere replication. 相似文献
16.
In the present paper the chromosome complement (n = 13; 2n = 26) of the common leech Haemopis sanguisuga (L.) (Annelida: Hirudinea: Hirudinidae) was analyzed using banding techniques and fluorescent in situ hybridization (FISH) with three repetitive DNA probes [ribosomal DNA (rDNA), (TTAGGG)
n
and (GATA)
n
]. FISH with the rDNA probe consistently mapped major ribosomal clusters (18S–28S rDNA) in the pericentromeric region of one large metacentric chromosome pair; this region, which consisted of heterochromatin rich in GC base pairs, was preferentially stained by silver nitrate (Ag-NOR). The (TTAGGG)
n
telomeric probe was hybridized with the termini of nearly all chromosomes, whereas the (GATA)
n
probe did not label any chromosome areas. 相似文献
17.
Dmitry Kaluzhny Anna ShchyolkinaMichael Livshits Yury LysovOlga Borisova 《Biophysical chemistry》2009
Human genome is shown to be enriched with (GT)n stretches of lengths from 8 to 20 dinucleotides. Low temperature (T ≤ 10 °C) conformations of d(GT)n oligonucleotides (n = 7, 8, 12, 16, 20) were studied by means of circular dichroism (CD), thermal melting, ethidium bromide (EtBr) probing and single nucleotide substitutions. Rotational relaxation times for EtBr:d(GT)n complexes confirmed a monomolecular state of the oligonucleotides. CD spectra indicated involvement of all guanines of d(GT)8 and d(GT)16 in G-quartets, while dT(GT)7, d(GT)12 and d(GT)20 were shown to be only partially ordered. The schemes of the d(GT)8 and d(GT)16 folds are suggested. 相似文献
18.
Irina A. Beschetnova Dmitry N. Kaluzhny Mikhail A. Livshits Anna K. Shchyolkina Olga F. Borisova 《Journal of biomolecular structure & dynamics》2013,31(6):789-799
Abstract Oligonucleotides 3′-d(GT)5-(CH2CH2O)3-d(GT)5-3′ (parGT), containing GT repeats present in the telomeric DNA from Saccharomyces cerevisiae, had been demonstrated to form bimolecular structure, GT-quadruplex (qGT) [O. F. Borisova et al. FEBS Letters 306, 140–142 (1992)]. Four d(GT)5 strands of the GT-quadruplex are parallel and form five G-quartets while thymines are bulged out. The four GT repeats when flanked by guanines, 3′-dG(TG)4G-(CH2CH2O)3- dG(GT)4G-3′ (hp-GT), had been shown to form a novel parallel-stranded (ps) double helix with G·G and T·T base pairs (hp-GT ps-DNA) [A. K. Shchyolkina et al. J. Biomol. Struct. Dynam. 18, 493–503 (2001)]. In the present study the intercalator ethidium bromide (Et) was used for probing the two structures. The mode of Et binding and its effect on thermostability of qGT and hp-GT were compared. The quantum yield (q) and the fluorescence lifetime (τ) of Et:qGT (q = 0.15 ±0.01 and τ = 24 ±1 ns) and Et:hp-GT (q = 0.10 ± 0.01 and τ = 16.5 ± 1 ns) indicative of intercalation mode of Et binding were determined. Et binding to qGT was found to be cooperative with corresponding coefficient ω = 3.9 ± 0.1 and the binding constant K= (6.4 ± 0.1)·10M?1. The maximum number of Et molecules intercalating into GT-quadruplex is as high as twice the number of inerspaces between G-quartets (eight in our case). The data conform to the model of Et association with GT-quadruplex suggested earlier [O. F. Borisova et al. Mol. Biol. (Russ) 35, 732–739 (2001)]. The anticooperative type of Et binding was observed in case of hp- GT ps-DNA, with the maximum number of bound Et molecules, N = 4 ÷ 5, and the association constant K = (1.5 ± 0.1)·105 M?1. Thermodynamic parameters of formation of Et:qGT and EtBr:hp-GT complexes were calculated from UV thermal denaturation profiles. 相似文献
19.
20.
Simone Carrino Christopher D Hennecker Ana C Murrieta Anthony Mittermaier 《Nucleic acids research》2021,49(6):3063
Human chromosomes terminate in long, single-stranded, DNA overhangs of the repetitive sequence (TTAGGG)n. Sets of four adjacent TTAGGG repeats can fold into guanine quadruplexes (GQ), four-stranded structures that are implicated in telomere maintenance and cell immortalization and are targets in cancer therapy. Isolated GQs have been studied in detail, however much less is known about folding in long repeat sequences. Such chains adopt an enormous number of configurations containing various arrangements of GQs and unfolded gaps, leading to a highly frustrated energy landscape. To better understand this phenomenon, we used mutagenesis, thermal melting, and global analysis to determine stability, kinetic, and cooperativity parameters for GQ folding within chains containing 8–12 TTAGGG repeats. We then used these parameters to simulate the folding of 32-repeat chains, more representative of intact telomeres. We found that a combination of folding frustration and negative cooperativity between adjacent GQs increases TTAGGG unfolding by up to 40-fold, providing an abundance of unfolded gaps that are potential binding sites for telomeric proteins. This effect was most pronounced at the chain termini, which could promote telomere extension by telomerase. We conclude that folding frustration is an important and largely overlooked factor controlling the structure of telomeric DNA. 相似文献