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Crystal structures of a DNA octaplex with I-motif of G-quartets and its splitting into two quadruplexes suggest a folding mechanism of eight tandem repeats.

ABSTRACT: Recent genomic analyses revealed many kinds of tandem repeats of specific sequences. Some of them are related to genetic diseases, but their biological functions and structures are still unknown. Two X-ray structures of a short DNA fragment d(gcGA[G]1Agc) show that four base-intercalated duplexes are assembled to form an octaplex at a low K+ concentration, in which the eight G5 residues form a stacked double G-quartet in the central part. At a higher K+ concentration, however, the octaplex is split into just two halves. These structural features suggest a folding process of eight tandem repeats of d(ccGA[G]4Agg), according to a double Greek-key motif. Such a packaging of the repeats could facilitate slippage of a certain sequence during DNA replication, to induce increase or decrease of the repeats.

SUBMITTER: Kondo J

PROVIDER: S-EPMC419463 | biostudies-literature | 2004

REPOSITORIES: biostudies-literature

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Crystal structures of a DNA octaplex with I-motif of G-quartets and its splitting into two quadruplexes suggest a folding mechanism of eight tandem repeats.

Kondo Jiro J Adachi Wataru W Umeda Shun-ichi S Sunami Tomoko T Takénaka Akio A

Nucleic acids research 20040507 8

Recent genomic analyses revealed many kinds of tandem repeats of specific sequences. Some of them are related to genetic diseases, but their biological functions and structures are still unknown. Two X-ray structures of a short DNA fragment d(gcGA[G]1Agc) show that four base-intercalated duplexes are assembled to form an octaplex at a low K+ concentration, in which the eight G5 residues form a stacked double G-quartet in the central part. At a higher K+ concentration, however, the octaplex is sp ...[more]

PMID: 15133122

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Project description:BACKGROUND: Tandem repetition of structural motifs in proteins is frequently observed across all forms of life. Topology of repeating unit and its frequency of occurrence are associated to a wide range of structural and functional roles in diverse proteins, and defects in repeat proteins have been associated with a number of diseases. It is thus desirable to accurately identify specific repeat type and its copy number. Weak evolutionary constraints on repeat units and insertions/deletions between them make their identification difficult at the sequence level and structure based approaches are desired. The proposed graph spectral approach is based on protein structure represented as a graph for detecting one of the most frequently observed structural repeats, Ankyrin repeat. RESULTS: It has been shown in a large number of studies that 3-dimensional topology of a protein structure is well captured by a graph, making it possible to analyze a complex protein structure as a mathematical entity. In this study we show that eigen spectra profile of a protein structure graph exhibits a unique repetitive profile for contiguous repeating units enabling the detection of the repeat region and the repeat type. The proposed approach uses a non-redundant set of 58 Ankyrin proteins to define rules for the detection of Ankyrin repeat motifs. It is evaluated on a set of 370 proteins comprising 125 known Ankyrin proteins and remaining non-solenoid proteins and the prediction compared with UniProt annotation, sequence-based approach, RADAR, and structure-based approach, ConSole. To show the efficacy of the approach, we analyzed the complete PDB structural database and identified 641 previously unrecognized Ankyrin repeat proteins. We observe a unique eigen spectra profile for different repeat types and show that the method can be easily extended to detect other repeat types. It is implemented as a web server, AnkPred. It is freely available at 'bioinf.iiit.ac.in/AnkPred'. CONCLUSIONS: AnkPred provides an elegant and computationally efficient graph-based approach for detecting Ankyrin structural repeats in proteins. By analyzing the eigen spectra of the protein structure graph and secondary structure information, characteristic features of a known repeat family are identified. This method is especially useful in correctly identifying new members of a repeat family.

Project description:BackgroundTandem repeats are ubiquitous and abundant in higher eukaryotic genomes and constitute, along with transposable elements, much of DNA underlying centromeres and other heterochromatic domains. In maize, centromeric satellite repeat (CentC) and centromeric retrotransposons (CR), a class of Ty3/gypsy retrotransposons, are enriched at centromeres. Some satellite repeats have homology to retrotransposons and several mechanisms have been proposed to explain the expansion, contraction as well as homogenization of tandem repeats. However, the origin and evolution of tandem repeat loci remain largely unknown.ResultsCRM1TR and CRM4TR are novel tandem repeats that we show to be entirely derived from CR elements belonging to two different subfamilies, CRM1 and CRM4. Although these tandem repeats clearly originated in at least two separate events, they are derived from similar regions of their respective parent element, namely the long terminal repeat (LTR) and untranslated region (UTR). The 5' ends of the monomer repeat units of CRM1TR and CRM4TR map to different locations within their respective LTRs, while their 3' ends map to the same relative position within a conserved region of their UTRs. Based on the insertion times of heterologous retrotransposons that have inserted into these tandem repeats, amplification of the repeats is estimated to have begun at least ~4 (CRM1TR) and ~1 (CRM4TR) million years ago. Distinct CRM1TR sequence variants occupy the two CRM1TR loci, indicating that there is little or no movement of repeats between loci, even though they are separated by only ~1.4 Mb.ConclusionsThe discovery of two novel retrotransposon derived tandem repeats supports the conclusions from earlier studies that retrotransposons can give rise to tandem repeats in eukaryotic genomes. Analysis of monomers from two different CRM1TR loci shows that gene conversion is the major cause of sequence variation. We propose that successive intrastrand deletions generated the initial repeat structure, and gene conversions increased the size of each tandem repeat locus.

Dataset Information

Crystal structures of a DNA octaplex with I-motif of G-quartets and its splitting into two quadruplexes suggest a folding mechanism of eight tandem repeats.

Publications

Crystal structures of a DNA octaplex with I-motif of G-quartets and its splitting into two quadruplexes suggest a folding mechanism of eight tandem repeats.

Similar Datasets

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