Molecular crowding of the cosolutes induces an intramolecular i-motif structure of triplet repeat DNA oligomers at neutral pH.

We now present the first example in which triplet repeat DNAs adopt the i-motif structure at neutral pH by molecular crowding. Crowding stabilized the i-motif and the pK(a) of N3 of cytosine was raised in such a microenvironment. Molecular crowding is known to accelerate the formation of the multi-stranded i-motif while the triplet repeats adopt the single-strand structure.

[1]  S. Mariappan,et al.  Structure and dynamics of the DNA hairpins formed by tandemly repeated CTG triplets associated with myotonic dystrophy. , 1996, Nucleic acids research.

[2]  Shi-jie Chen,et al.  Salt dependence of nucleic acid hairpin stability. , 2008, Biophysical journal.

[3]  N. Sugimoto,et al.  Molecular crowding effects on structure and stability of DNA. , 2008, Biochimie.

[4]  V. Bloomfield,et al.  Crowding effects on EcoRV kinetics and binding. , 1999, Biophysical journal.

[5]  G. Riggins,et al.  Human genes containing polymorphic trinucleotide repeats , 1992, Nature Genetics.

[6]  Allen P. Minton,et al.  Cell biology: Join the crowd , 2003, Nature.

[7]  R. Sinden,et al.  DNA structure, mutations, and human genetic disease. , 1992, Current opinion in biotechnology.

[8]  A. Minton.  Excluded volume as a determinant of macromolecular structure and reactivity , 1981 .

[9]  M. Katahira,et al.  Intramolecular Higher Order Packing of Parallel Quadruplexes Comprising a G:G:G:G Tetrad and a G(:A):G(:A):G(:A):G Heptad of GGA Triplet Repeat DNA* , 2003, Journal of Biological Chemistry.

[10]  A. Minton,et al.  The Influence of Macromolecular Crowding and Macromolecular Confinement on Biochemical Reactions in Physiological Media* , 2001, The Journal of Biological Chemistry.

[11]  H. Yamazaki,et al.  A single-stranded DNA binding protein from mouse tumor cells specifically recognizes the C-rich strand of the (AGG:CCT)n repeats that can alter DNA conformation. , 1992, Nucleic acids research.

[12]  A. Minton,et al.  Macromolecular crowding: biochemical, biophysical, and physiological consequences. , 1993, Annual review of biophysics and biomolecular structure.

[13]  X. Qu,et al.  Single-walled carbon nanotubes binding to human telomeric i-motif DNA under molecular-crowding conditions: more water molecules released. , 2008, Chemistry.

[14]  Huntington F. Willard,et al.  Hierarchical order in chromosome-specific human alpha satellite DNA , 1987 .

[15]  Damien Hall,et al.  Macromolecular crowding: qualitative and semiquantitative successes, quantitative challenges. , 2003, Biochimica et biophysica acta.

[16]  J. Leroy,et al.  Intramolecular Folding of Pyrimidine Oligodeoxynucleotides into an i-DNA Motif , 1995 .

[17]  R. Wells,et al.  Intramolecular DNA triplexes in supercoiled plasmids. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[18]  L. Hurley,et al.  Intramolecularly folded G-quadruplex and i-motif structures in the proximal promoter of the vascular endothelial growth factor gene , 2008, Nucleic acids research.

[19]  J. Weber,et al.  Survey of human and rat microsatellites. , 1992, Genomics.

[20]  Guliang Wang,et al.  Non-B DNA structure-induced genetic instability. , 2006, Mutation research.

[21]  Aleksandar Milosavljevic,et al.  Abundance and length of simple repeats in vertebrate genomes are determined by their structural properties. , 2008, Genome research.

[22]  N. Sugimoto,et al.  Duplex dissociation of telomere DNAs induced by molecular crowding. , 2004, Journal of the American Chemical Society.

[23]  N. Sugimoto,et al.  Molecular crowding regulates the structural switch of the DNA G-quadruplex. , 2002, Biochemistry.