Formation of Pearl-Necklace Monomorphic G-Quadruplexes in the Human CEB25 Minisatellite

CEB25 is a human minisatellite locus, composed of slightly polymorphic 52-nucleotide (nt) tandem repeats. Genetically, most if not all individuals of the human population are heterozygous, carrying alleles ranging from 0.5 to 20 kb, maintained by mendelian inheritance but also subject to germline in...

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Published in	Journal of the American Chemical Society Vol. 134; no. 13; pp. 5807 - 5816
Main Authors	Amrane, Samir, Adrian, Michael, Heddi, Brahim, Serero, Alexandre, Nicolas, Alain, Mergny, Jean-Louis, Phan, Anh Tuân
Format	Journal Article
Language	English
Published	United States American Chemical Society 04.04.2012
Subjects	alleles Base Pairing Base Sequence enthalpy G-Quadruplexes Genetic Loci - genetics germ cells heterozygosity human population Humans loci melting point Mendelian inheritance Minisatellite Repeats - genetics Models, Molecular nuclear magnetic resonance spectroscopy Nucleic Acid Denaturation potassium Potassium - chemistry Solutions tandem repeat sequences Thermodynamics Transition Temperature
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Abstract	CEB25 is a human minisatellite locus, composed of slightly polymorphic 52-nucleotide (nt) tandem repeats. Genetically, most if not all individuals of the human population are heterozygous, carrying alleles ranging from 0.5 to 20 kb, maintained by mendelian inheritance but also subject to germline instability. To provide insights on the biological role of CEB25, we interrogated its structural features. We report the NMR structure of the G-quadruplex formed by the conserved 26-nt G-rich fragment of the CEB25 motif. In K+ solution, this sequence forms a propeller-type parallel-stranded G-quadruplex involving a 9-nt central double-chain-reversal loop. This long loop is anchored to the 5′-end of the sequence by an A·T Watson–Crick base pair and a potential G·A noncanonical base pair. These base pairs contribute to the stability of the overall G-quadruplex structure, as measured by an increase of about 17 kcal/mol in enthalpy or 6 °C in melting temperature. Further, we demonstrate that such a monomorphic structure is formed within longer sequence contexts folding into a pearl-necklace structure.
AbstractList	CEB25 is a human minisatellite locus, composed of slightly polymorphic 52-nucleotide (nt) tandem repeats. Genetically, most if not all individuals of the human population are heterozygous, carrying alleles ranging from 0.5 to 20 kb, maintained by mendelian inheritance but also subject to germline instability. To provide insights on the biological role of CEB25, we interrogated its structural features. We report the NMR structure of the G-quadruplex formed by the conserved 26-nt G-rich fragment of the CEB25 motif. In K+ solution, this sequence forms a propeller-type parallel-stranded G-quadruplex involving a 9-nt central double-chain-reversal loop. This long loop is anchored to the 5′-end of the sequence by an A·T Watson–Crick base pair and a potential G·A noncanonical base pair. These base pairs contribute to the stability of the overall G-quadruplex structure, as measured by an increase of about 17 kcal/mol in enthalpy or 6 °C in melting temperature. Further, we demonstrate that such a monomorphic structure is formed within longer sequence contexts folding into a pearl-necklace structure. CEB25 is a human minisatellite locus, composed of slightly polymorphic 52-nucleotide (nt) tandem repeats. Genetically, most if not all individuals of the human population are heterozygous, carrying alleles ranging from 0.5 to 20 kb, maintained by mendelian inheritance but also subject to germline instability. To provide insights on the biological role of CEB25, we interrogated its structural features. We report the NMR structure of the G-quadruplex formed by the conserved 26-nt G-rich fragment of the CEB25 motif. In K⁺ solution, this sequence forms a propeller-type parallel-stranded G-quadruplex involving a 9-nt central double-chain-reversal loop. This long loop is anchored to the 5′-end of the sequence by an A·T Watson–Crick base pair and a potential G·A noncanonical base pair. These base pairs contribute to the stability of the overall G-quadruplexstructure, as measured by an increase of about 17 kcal/mol in enthalpy or 6 °C in melting temperature. Further, we demonstrate that such a monomorphic structure is formed within longer sequence contexts folding into a pearl-necklace structure. CEB25 is a human minisatellite locus, composed of slightly polymorphic 52-nucleotide (nt) tandem repeats. Genetically, most if not all individuals of the human population are heterozygous, carrying alleles ranging from 0.5 to 20 kb, maintained by mendelian inheritance but also subject to germline instability. To provide insights on the biological role of CEB25, we interrogated its structural features. We report the NMR structure of the G-quadruplex formed by the conserved 26-nt G-rich fragment of the CEB25 motif. In K(+) solution, this sequence forms a propeller-type parallel-stranded G-quadruplex involving a 9-nt central double-chain-reversal loop. This long loop is anchored to the 5'-end of the sequence by an A·T Watson-Crick base pair and a potential G·A noncanonical base pair. These base pairs contribute to the stability of the overall G-quadruplexstructure, as measured by an increase of about 17 kcal/mol in enthalpy or 6 °C in melting temperature. Further, we demonstrate that such a monomorphic structure is formed within longer sequence contexts folding into a pearl-necklace structure.CEB25 is a human minisatellite locus, composed of slightly polymorphic 52-nucleotide (nt) tandem repeats. Genetically, most if not all individuals of the human population are heterozygous, carrying alleles ranging from 0.5 to 20 kb, maintained by mendelian inheritance but also subject to germline instability. To provide insights on the biological role of CEB25, we interrogated its structural features. We report the NMR structure of the G-quadruplex formed by the conserved 26-nt G-rich fragment of the CEB25 motif. In K(+) solution, this sequence forms a propeller-type parallel-stranded G-quadruplex involving a 9-nt central double-chain-reversal loop. This long loop is anchored to the 5'-end of the sequence by an A·T Watson-Crick base pair and a potential G·A noncanonical base pair. These base pairs contribute to the stability of the overall G-quadruplexstructure, as measured by an increase of about 17 kcal/mol in enthalpy or 6 °C in melting temperature. Further, we demonstrate that such a monomorphic structure is formed within longer sequence contexts folding into a pearl-necklace structure. CEB25 is a human minisatellite locus, composed of slightly polymorphic 52-nucleotide (nt) tandem repeats. Genetically, most if not all individuals of the human population are heterozygous, carrying alleles ranging from 0.5 to 20 kb, maintained by mendelian inheritance but also subject to germline instability. To provide insights on the biological role of CEB25, we interrogated its structural features. We report the NMR structure of the G-quadruplex formed by the conserved 26-nt G-rich fragment of the CEB25 motif. In K(+) solution, this sequence forms a propeller-type parallel-stranded G-quadruplex involving a 9-nt central double-chain-reversal loop. This long loop is anchored to the 5'-end of the sequence by an A·T Watson-Crick base pair and a potential G·A noncanonical base pair. These base pairs contribute to the stability of the overall G-quadruplexstructure, as measured by an increase of about 17 kcal/mol in enthalpy or 6 °C in melting temperature. Further, we demonstrate that such a monomorphic structure is formed within longer sequence contexts folding into a pearl-necklace structure.
Author	Serero, Alexandre Adrian, Michael Mergny, Jean-Louis Nicolas, Alain Phan, Anh Tuân Amrane, Samir Heddi, Brahim
AuthorAffiliation	University of Bordeaux Nanyang Technological University Université Pierre et Marie Curie
AuthorAffiliation_xml	– name: Université Pierre et Marie Curie – name: Nanyang Technological University – name: University of Bordeaux
Author_xml	– sequence: 1 givenname: Samir surname: Amrane fullname: Amrane, Samir – sequence: 2 givenname: Michael surname: Adrian fullname: Adrian, Michael – sequence: 3 givenname: Brahim surname: Heddi fullname: Heddi, Brahim – sequence: 4 givenname: Alexandre surname: Serero fullname: Serero, Alexandre – sequence: 5 givenname: Alain surname: Nicolas fullname: Nicolas, Alain – sequence: 6 givenname: Jean-Louis surname: Mergny fullname: Mergny, Jean-Louis email: phantuan@ntu.edu.sg, jean-louis.mergny@inserm.fr – sequence: 7 givenname: Anh Tuân surname: Phan fullname: Phan, Anh Tuân email: phantuan@ntu.edu.sg, jean-louis.mergny@inserm.fr
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/22376028$$D View this record in MEDLINE/PubMed
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Snippet	CEB25 is a human minisatellite locus, composed of slightly polymorphic 52-nucleotide (nt) tandem repeats. Genetically, most if not all individuals of the human...
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SubjectTerms	alleles Base Pairing Base Sequence enthalpy G-Quadruplexes Genetic Loci - genetics germ cells heterozygosity human population Humans loci melting point Mendelian inheritance Minisatellite Repeats - genetics Models, Molecular nuclear magnetic resonance spectroscopy Nucleic Acid Denaturation potassium Potassium - chemistry Solutions tandem repeat sequences Thermodynamics Transition Temperature
Title	Formation of Pearl-Necklace Monomorphic G-Quadruplexes in the Human CEB25 Minisatellite
URI	http://dx.doi.org/10.1021/ja208993r https://www.ncbi.nlm.nih.gov/pubmed/22376028 https://www.proquest.com/docview/2000355913 https://www.proquest.com/docview/968104835
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