| >> The Torigoe Lab | >> Research | >> Members | >> Publications |
| >> Lab Contact Info | >> Links | >> Japanese |
<< Research >>
< Research Topics >
Biochemistry, Molecular Biology, and Structural Biology in the Postgenome Era
In the postgenome era, Torigoe Research Group is focusing on the life events
in the nucleus based on the genetic information. The main research topics
are as follows:
1) Development of Novel Strategy to Artificially Regulate Gene Expression
by Triplex Nucleic Acid Formation:
A triplex nucleic acid is formed through the sequence-specific interaction
between the homopurine-homopyrimidine stretch in duplex DNA and a single-stranded
homopyrimidine or homopurine oligonucleotide. Triplex formation has the
potential to be applied to artificial regulation of transcription as antigene
strategy. However, extreme instability of the triplex under physiological
condition severely limits the therapeutic potential of the triplex. Thus,
stabilization of the triplex under physiological condition is necessary
for improving its therapeutic potential. We are developing the novel strategy
to stabilize the triplex under physiological condition, which may lead
to progress in therapeutic applications of the antigene strategy in vivo.
References:
1) Torigoe, H., Rahman, S. M., Takuma, H., Sato, N., Imanishi, T., Obika,
S., and Sasaki, K.
" 2'-O,4'-C-Aminomethylene Bridged Nucleic Acid Modification with Enhancement of Nuclease
Resistance Promotes Pyrimidine Motif Triplex Nucleic Acid Formation at
Physiological pH "
Chemistry – A European Journal, 17(9), 2742-2751 (2011). [PubMed]
2) Torigoe, H., Rahman, S. M., Takuma, H., Sato, N., Imanishi, T., Obika,
S., and Sasaki, K.
" Interrupted 2'-O,4'-C-Aminomethylene Bridged Nucleic Acid Modification Enhances Pyrimidine Motif
Triplex-Forming Ability and Nuclease Resistance under Physiological Condition
"
Nucleosides, Nucleotides, & Nucleic Acids, 30(1), 63-81 (2011). [PubMed] [Journal site]
3) Torigoe, H., Maruyama, A., Obika, S., Imanishi, T., and Katayama, T.
" Synergistic Stabilization of Nucleic Acid Assembly by 2-O,4-C-Methylene Bridged Nucleic Acid Modification and Additions of Comb-type
Cationic Copolymers "
Biochemistry, 48(15), 3545-3553 (2009). [PubMed]
4) Torigoe, H., Sasaki, K., and Katayama, T.
" Thermodynamic and Kinetic Effects of Morpholino Modification on Pyrimidine Motif Triplex Nucleic Acid Formation under Physiological Condition "
J Biochem, 146(2), 173-183 (2009). [PubMed]
5) Torigoe, H., and Maruyama, A.
" Synergistic Stabilization of Nucleic Acid Assembly by Oligo-N3'-P5'
Phosphoramidate Modification and Additions of Comb-type Cationic Copolymers
"
J. Am. Chem. Soc., 127, 1705-1710 (2005). [PubMed]
2) Development of Novel Method to Efficiently Detect Single Nucleotide
Polymorphism (SNP):
Single nucleotide polymorphism (SNP) is the most abundant form of genetic
variation in the human genomic DNA, accounting for most of all differences
between individuals. Analyses of SNP can help to identify genes affecting
many human phenotype variations, including complex diseases and drug responses.
We are developing the novel strategy to efficiently detect SNP by the specific
interaction between metal cation and mismatch base pair, which we have
found recently.
References:
1) Torigoe, H., Miyakawa, Y., Ono, A., and Kozasa, T.
" Positive Cooperativity of the Specific Binding between Hg2+ Ion and T:T Mismatched Base Pairs in Duplex DNA "
Thermochimica Acta, in press. [Journal site]
2) Torigoe, H., Miyakawa, Y., Ono, A., and Kozasa, T.
" Thermodynamic Properties of the Specific Binding between Ag+ Ions and C:C Mismatched Base Pairs in Duplex DNA "
Nucleosides, Nucleotides, & Nucleic Acids, 30(2), 149-167 (2011). [PubMed] [Journal site]
3) Torigoe, H., Ono, A., and Kozasa, T.
" Detection of Single Nucleotide Polymorphisms by the Specific Interaction
between Transition Metal Ions and Mismatched Base Pairs in Duplex DNA "
Transition Metal Chemistry, 36(2), 131-144 (2011). [Journal site]
4) Torigoe, H., Ono, A., and Kozasa, T.
" HgII Ion Specifically Binds with T:T Mismatched Base Pair in Duplex DNA "
Chemistry – A European Journal, 16(44), 13218-13225 (2010). [PubMed]
5) Torigoe, H., Kawahashi, K., Takamori, A., and Ono, A.
" Novel Strategy for Single Nucleotide Polymorphism (SNP) Genotyping
by Heteroduplex Analysis: Specific Stabilization of TT Mismatch Base Pair
by Mercury (II) Cation and CC Mismatch Base Pair by Silver (I) Cation "
Nucleosides Nucleotides Nucleic Acids, 24, 915-917 (2005). [PubMed] [Journal site]
3) Investigation on Telomeric Length Regulation Mechanism to Reveal the
Mechanism of Cellular Aging and Tumorgenesis:
Telomere at the ends of linear eukaryotic chromosomes is essential for maintaining chromosomal stability. Telomeric DNA consists of tandemly repeated sequences, one strand being rich in guanines. The length of telomeric DNA strongly correlates with cellular aging and cancer, and it is regulated by telomere binding proteins and telomerase. We are investigating the telomeric length regulation mechanism by the structural and functional analyses of telomere binding proteins and telomerase.
References:
1) Torigoe, H., and Furukawa, A.
" Tetraplex Structure of Fission Yeast Telomeric DNA and Unfolding
of the Tetraplex on the Interaction with Telomeric DNA Binding Protein
Pot1 "
J. Biochem., 141, 57-68 (2007). [PubMed]
2) Torigoe, H., Dohmae, N., Hanaoka, F., and Furukawa, A.
" Mutational Analyses of a Single-stranded Telomeric DNA Binding Domain
of Fission Yeast Pot1: Conflict with X-ray Crystallographic Structure "
Biosci. Biotech. Biochem., 71, 481-490 (2007). [PubMed]
< Highlights >
1) We have found that 2'-O,4'-C-aminomethylene bridged nucleic acid (2', 4'-BNANC) modification of triplex forming oligonucleotide is quite useful to stabilize
the triplex under physiological condition. The 2', 4'-BNANC modification can be a key chemical modification, and may lead to progress
in therapeutic applications of the antigene strategy in vivo.
2) We have found that mercury (II) cation specifically binds with T:T mismatch base pair, and silver (I) cation specifically binds with C:C mismatch base pair. These specific interactions between metal cation and mismatch base pair can be applied to the detection of SNP.
3) We have found that mouse single-stranded telomeric DNA binding protein Pot1 has the ability to unfold the tetraplex of mouse telomeric DNA, where four guanines align with each other through non-Watson-Crick G:G base pair hydrogen bonds to form a square planar configuration. Considering that the tetraplex inhibits telomerase-mediated telomere elongation, the ability of Pot1 to unfold the tetraplex of the telomeric DNA is required for telomerase-mediated telomere elongation.
Last modified on March 28, 2011
This site is maintained by Tetsuo Kozasa
COPYRIGHT © 2006-2010, TOKYO UNIVERSITY OF SCIENCE, TORIGOE RESEARCH GROUP, ALL RIGHTS RESERVED.