Influence of pH, temperature and the cationic porphyrin TMPyP4 on the stability of the i-motif formed by the 5′-(C3TA2)4-3′ sequence of the human telomere

Fernández, Susana; Eritja, Ramón; Aviñó, Anna; Jaumot, Joaquim; Gargallo, Raimundo

doi:10.1016/j.ijbiomac.2011.07.004

Cited by 49 publications

(52 citation statements)

References 40 publications

(51 reference statements)

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“…Generally,t his effect is destabilizing because protonation at the N1 position disrupts Watson-Crick base pairs. [13,31] In our case, adenine protonation in N1 results in stabilizationo fa nA:T Hoogsteen base pair,p robably due to acidification of the adenine amino protons, enabling them to form strongerh ydrogen bonds. This stabilization of Hoogsteen base pair upon adenine protonation has been reported in some RNA molecules such as the hairpin ribozyme.…”

Section: Discussionmentioning

confidence: 69%

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Centromeric Alpha‐Satellite DNA Adopts Dimeric i‐Motif Structures Capped by AT Hoogsteen Base Pairs

Garavís

Escaja

Gabelica

et al. 2015

Chemistry A European J

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International audience© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Human centromeric alpha-satellite DNA is composed of tandem arrays of two types of 171 bp monomers; type A and type B. The differences between these types are concentrated in a 17 bp region of the monomer called the A/B box. Here, we have determined the solution structure of the C-rich strand of the two main variants of the human alpha-satellite A box. We show that, under acidic conditions, the C-rich strands of two A boxes self-recognize and form a head-to-tail dimeric i-motif stabilized by four intercalated hemi-protonated C:C + base pairs. Interestingly, the stack of C:C + base pairs is capped by T:T and Hoogsteen A:T base pairs. The two main variants of the A box adopt a similar three-dimensional structure, although the residues involved in the formation of the i-motif core are different in each case. Together with previous studies showing that the B box (known as the CENP-B box) also forms dimeric i-motif structures, our finding of this non-canonical structure in the A box shows that centromeric alpha satellites in all human chromosomes are able to form i-motifs, which consequently raises the possibility that these structures may play a role in the structural organization of the centromere. Nucleosome organization: All human centromeric alpha-satellites contain sequences that can form dimeric i-motif structures in vitro (see figure). These regions occur every 171 bp and are found at the entrance and exit of the nucleosome. This finding suggests that the i-motif may play a role in the higher order nucleosome organization at the centromere. ; Peer Reviewe

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Section: Discussionmentioning

confidence: 69%

“…[28] A:Tb ase pairs are not so common,b ut they have also been observed in monomeric [13,28,29] and tetrameric i-motifs. [30] In some cases, adenine protonation affects the structure [13,31] and the stability of the i-motif. Generally,t his effect is destabilizing because protonation at the N1 position disrupts Watson-Crick base pairs.…”

Section: Discussionmentioning

confidence: 99%

Centromeric Alpha‐Satellite DNA Adopts Dimeric i‐Motif Structures Capped by AT Hoogsteen Base Pairs

Garavís

Escaja

Gabelica

et al. 2015

Chemistry A European J

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“…If some unmethylated cytosines do not react with bisulfite, they will be detected as methylated cytosines leading to overestimation of the methylation events. Thus, overestimation of telomeric methylation should be influenced by the degree of telomeric DNA denaturation or the formation of telomeric C-rich strand secondary structures like the imotif (Leroy et al 1994;Fernández et al 2011;Guo et al 2013). In addition, since bisulfite treatment modifies DNA and even degrades it (Frommer et al 1992;Grunau et al 2001), some unmethylated cytosines might partially or improperly react with bisulfite reagents leading to the generation of aberrant cytosines.…”

Section: Discussion Limitations Of the Bisulfite Sequencing Techniquementioning

confidence: 99%

Novel features of telomere biology revealed by the absence of telomeric DNA methylation

et al. 2016

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Cytosine methylation regulates the length and stability of telomeres, which can affect a wide variety of biological features, including cell differentiation, development, or illness. Although it is well established that subtelomeric regions are methylated, the presence of methylated cytosines at telomeres has remained controversial. Here, we have analyzed multiple bisulfite sequencing studies to address the methylation status of Arabidopsis thaliana telomeres. We found that the levels of estimated telomeric DNA methylation varied among studies. Interestingly, we estimated higher levels of telomeric DNA methylation in studies that produced C-rich telomeric strands with lower efficiency. However, these high methylation estimates arose due to experimental limitations of the bisulfite technique. We found a similar phenomenon for mitochondrial DNA: The levels of mitochondrial DNA methylation detected were higher in experiments with lower mitochondrial read production efficiencies. Based on experiments with high telomeric C-rich strand production efficiencies, we concluded that Arabidopsis telomeres are not methylated, which was confirmed by methylation-dependent restriction enzyme analyses. Thus, our studies indicate that telomeres are refractory to de novo DNA methylation by the RNA-directed DNA methylation machinery. This result, together with previously reported data, reveals that subtelomeric DNA methylation controls the homeostasis of telomere length.[Supplemental material is available for this article.]Telomeres guarantee the complete replication of chromosomal termini, prevent genome instability, and influence relevant systemic processes like aging, cancer, or illness (Blackburn 2010). The length of telomeres and the chromatin organization of telomeric regions influence telomere functions. Hence, the epigenetic marks that label telomeric regions, which include telomeres and subtelomeres, play important roles in telomere biology (Blasco 2007;Galati et al. 2013;Giraud-Panis et al. 2013).One of the major epigenetic signatures found in eukaryotes is cytosine methylation. This DNA modification regulates multiple processes in plants and animals, including the homeostasis of telomere length (Blasco 2007;Suzuki and Bird 2008;Ooi et al. 2009;Law and Jacobsen 2010;Castel and Martienssen 2013;Ogrocká et al. 2014;Vaquero-Sedas and Vega-Palas 2014). Mammalian DNA methylation is primarily found in the CG context (Ramsahoye et al. 2000;Lister et al. 2009). In contrast, plants have significant levels of DNA methylation in all sequence contexts (CG, CHG, and CHH, where H can be A, C, or T) (Law and Jacobsen 2010).Although subtelomeric DNA methylation has been reported in animals and plants, the presence of DNA methylation at telomeres remains an open question in both kingdoms (Blasco 2007;Vrbsky et al. 2010;Vaquero-Sedas et al. 2011;Ogrocká et al. 2014). The methylation status of mammalian telomeres has not been investigated because, as mentioned above, mammals have low levels of non-CG methylation, which is the type of DNA me...

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“…Hard-modeling of melting experiments was conducted using a modified version of the Multivariate Curve ResolutionAlternating Least Squares (MCR-ALS) procedure, which includes the model proposed in equation (4) for the unfolding of intramolecular structures [30].…”

Section: Discussionmentioning

confidence: 99%

“…This procedure is based on the proposal of thermodynamic equations to which spectroscopic data are fitted [30]. As example, the analysis of spectra recorded during a melting experiment at pH 6.1 is included as Supplementary Material ( Figure S2).…”

Section: Solution Equilibria Of the Cytosine-rich Regionmentioning

confidence: 99%

Solution equilibria of cytosine- and guanine-rich sequences near the promoter region of the n-myc gene that contain stable hairpins within lateral loops

Benabou

Ferreira

Aviñó

et al. 2014

Biochimica et Biophysica Acta (BBA) - General Subjects

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Influence of pH, temperature and the cationic porphyrin TMPyP4 on the stability of the i-motif formed by the 5′-(C3TA2)4-3′ sequence of the human telomere

Cited by 49 publications

References 40 publications

Centromeric Alpha‐Satellite DNA Adopts Dimeric i‐Motif Structures Capped by AT Hoogsteen Base Pairs

Centromeric Alpha‐Satellite DNA Adopts Dimeric i‐Motif Structures Capped by AT Hoogsteen Base Pairs

Novel features of telomere biology revealed by the absence of telomeric DNA methylation

Solution equilibria of cytosine- and guanine-rich sequences near the promoter region of the n-myc gene that contain stable hairpins within lateral loops

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