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Stability and kinetics of G-quadruplex structures.

Lane AN, Chaires JB, Gray RD, Trent JO - Nucleic Acids Res. (2008)

Bottom Line: Significant gaps in the literature have been identified, that should be filled by a systematic study of well-defined quadruplexes not only to provide the basic understanding of stability both for design purposes, but also as it relates to in vivo occurrence of quadruplexes.Quadruplex structures fold and unfold comparatively slowly, and DNA unwinding events associated with transcription and replication may be operating far from equilibrium.The kinetics of formation and resolution of quadruplexes, and methodologies are discussed in the context of stability and their possible biological occurrence.

View Article: PubMed Central - PubMed

Affiliation: Structural Biology Program, JG Brown Cancer Center, University of Louisville, KY 40202, USA. anlane01@gwise.louisville.edu

ABSTRACT
In this review, we give an overview of recent literature on the structure and stability of unimolecular G-rich quadruplex structures that are relevant to drug design and for in vivo function. The unifying theme in this review is energetics. The thermodynamic stability of quadruplexes has not been studied in the same detail as DNA and RNA duplexes, and there are important differences in the balance of forces between these classes of folded oligonucleotides. We provide an overview of the principles of stability and where available the experimental data that report on these principles. Significant gaps in the literature have been identified, that should be filled by a systematic study of well-defined quadruplexes not only to provide the basic understanding of stability both for design purposes, but also as it relates to in vivo occurrence of quadruplexes. Techniques that are commonly applied to the determination of the structure, stability and folding are discussed in terms of information content and limitations. Quadruplex structures fold and unfold comparatively slowly, and DNA unwinding events associated with transcription and replication may be operating far from equilibrium. The kinetics of formation and resolution of quadruplexes, and methodologies are discussed in the context of stability and their possible biological occurrence.

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Chemical structures of G-quartets and quadruplexes. (A) Anticonformation (top left) and syn conformation (top right) of guanosine. (B) Inosine (left) and 7-deazaG (right) variations. (C) G-quartet with metal ion coordination to GO6.
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Figure 1: Chemical structures of G-quartets and quadruplexes. (A) Anticonformation (top left) and syn conformation (top right) of guanosine. (B) Inosine (left) and 7-deazaG (right) variations. (C) G-quartet with metal ion coordination to GO6.

Mentions: G-quadruplexes of repeat sequences of the kind AGnTm spontaneously fold into stable compact structures in solution, especially in the presence of K+. The resulting structures are compact, resistant to DNAses, generally have high melting temperatures, and appear to be dominated by the presence of the so-called G-quartet stacks (Figure 1). Such sequences are found in telomeres, and at a surprisingly high frequency in other parts of the genome, especially in promoters (1,2). There is now an immense literature on both the biology and physical properties of such sequences (3–6). The literature through the mid-1990s has been reviewed in a book (7). It is now believed by some that G-quadruplex oligonucleotide structures are important biological regulators, both in DNA and RNA (3–6,8–17).Figure 1.


Stability and kinetics of G-quadruplex structures.

Lane AN, Chaires JB, Gray RD, Trent JO - Nucleic Acids Res. (2008)

Chemical structures of G-quartets and quadruplexes. (A) Anticonformation (top left) and syn conformation (top right) of guanosine. (B) Inosine (left) and 7-deazaG (right) variations. (C) G-quartet with metal ion coordination to GO6.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2553573&req=5

Figure 1: Chemical structures of G-quartets and quadruplexes. (A) Anticonformation (top left) and syn conformation (top right) of guanosine. (B) Inosine (left) and 7-deazaG (right) variations. (C) G-quartet with metal ion coordination to GO6.
Mentions: G-quadruplexes of repeat sequences of the kind AGnTm spontaneously fold into stable compact structures in solution, especially in the presence of K+. The resulting structures are compact, resistant to DNAses, generally have high melting temperatures, and appear to be dominated by the presence of the so-called G-quartet stacks (Figure 1). Such sequences are found in telomeres, and at a surprisingly high frequency in other parts of the genome, especially in promoters (1,2). There is now an immense literature on both the biology and physical properties of such sequences (3–6). The literature through the mid-1990s has been reviewed in a book (7). It is now believed by some that G-quadruplex oligonucleotide structures are important biological regulators, both in DNA and RNA (3–6,8–17).Figure 1.

Bottom Line: Significant gaps in the literature have been identified, that should be filled by a systematic study of well-defined quadruplexes not only to provide the basic understanding of stability both for design purposes, but also as it relates to in vivo occurrence of quadruplexes.Quadruplex structures fold and unfold comparatively slowly, and DNA unwinding events associated with transcription and replication may be operating far from equilibrium.The kinetics of formation and resolution of quadruplexes, and methodologies are discussed in the context of stability and their possible biological occurrence.

View Article: PubMed Central - PubMed

Affiliation: Structural Biology Program, JG Brown Cancer Center, University of Louisville, KY 40202, USA. anlane01@gwise.louisville.edu

ABSTRACT
In this review, we give an overview of recent literature on the structure and stability of unimolecular G-rich quadruplex structures that are relevant to drug design and for in vivo function. The unifying theme in this review is energetics. The thermodynamic stability of quadruplexes has not been studied in the same detail as DNA and RNA duplexes, and there are important differences in the balance of forces between these classes of folded oligonucleotides. We provide an overview of the principles of stability and where available the experimental data that report on these principles. Significant gaps in the literature have been identified, that should be filled by a systematic study of well-defined quadruplexes not only to provide the basic understanding of stability both for design purposes, but also as it relates to in vivo occurrence of quadruplexes. Techniques that are commonly applied to the determination of the structure, stability and folding are discussed in terms of information content and limitations. Quadruplex structures fold and unfold comparatively slowly, and DNA unwinding events associated with transcription and replication may be operating far from equilibrium. The kinetics of formation and resolution of quadruplexes, and methodologies are discussed in the context of stability and their possible biological occurrence.

Show MeSH