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

被引:88
作者
Amrane, Samir [1 ,2 ]
Adrian, Michael [2 ]
Heddi, Brahim [2 ]
Serero, Alexandre [3 ]
Nicolas, Alain [3 ]
Mergny, Jean-Louis [1 ]
Anh Tuan Phan [2 ]
机构
[1] Univ Bordeaux, European Inst Chem & Biol, INSERM U869, F-33600 Pessac, France
[2] Nanyang Technol Univ, Sch Phys & Math Sci, Singapore 637371, Singapore
[3] Univ Paris 06, CNRS UMR3244, Ctr Rech, Inst Curie, F-75248 Paris, France
关键词
HUMAN TELOMERIC DNA; MEIOTIC RECOMBINATION; TRINUCLEOTIDE REPEATS; DEPENDENT ENERGETICS; TANDEM REPEATS; MYC PROMOTER; LONG; INSTABILITY; LOOP; STABILITY;
D O I
10.1021/ja208993r
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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 AT 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 degrees C in melting temperature. Further, we demonstrate that such a monomorphic structure is formed within longer sequence contexts folding into a pearl-necklace structure.
引用
收藏
页码:5807 / 5816
页数:10
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