Context-Sensitive Cleavage of Folded DNAs by Loop-Targeting bPNAs.

Biochemistry
Yufeng LiangDennis Bong

Abstract

Herein, we demonstrate context-dependent molecular recognition of DNA by synthetic bPNA iron and copper complexes, using oxidative backbone cleavage as a chemical readout for binding. Oligoethylenimine bPNAs displaying iron·EDTA or copper·phenanthroline sites were found to be efficient chemical nucleases for designed and native structured DNAs with T-rich single-stranded domains. Cleavage reactivity depends strongly on structural context, as strikingly demonstrated with DNA substrates of the form (GGGTTA)n. This repeat sequence from the human telomere is known to switch between parallel and antiparallel G-quadruplex (G4) topologies with a change from potassium to sodium buffer: notably, bPNA-copper complexes efficiently cleave long repeat sequences into ∼22-nucleotide portions in sodium, but not potassium, buffer. We hypothesize preferential cleavage of the antiparallel topology (Na+) over the parallel topology (K+) due to the greater accessibility of the TTA loop to bPNA in the antiparallel (Na+) form. Similar ion-sensitive telomere shortening upon treatment with bPNA nucleases can be observed in both isolated and intracellular DNA from PC3 cells by quantitative polymerase chain reaction. Live cell treatment was accompanied by...Continue Reading

References

Feb 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·G B Dreyer, P B Dervan
Mar 1, 1994·Nature Structural Biology·X ChenM Sundaralingam
Apr 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·N CarmiR R Breaker
Jan 1, 1997·Biopolymers·J SantaLucia, D H Turner
Jun 1, 1997·Current Opinion in Chemical Biology·R R Breaker
Sep 1, 1999·Proceedings of the National Academy of Sciences of the United States of America·R H GriffeyS T Crooke
Jan 29, 2000·Journal of Natural Products·S M Hecht
Aug 31, 2000·Organic Letters·G J SanjayanK N Ganesh
Apr 11, 2001·Proceedings of the National Academy of Sciences of the United States of America·A R Urbach, P B Dervan
Sep 27, 2001·Journal of the American Chemical Society·B Datta, B A Armitage
Dec 12, 2001·Current Opinion in Chemical Biology·J A Cowan
May 10, 2002·Nucleic Acids Research·Richard M Cawthon
Jun 7, 2002·Nature·Gary N ParkinsonStephen Neidle
Apr 3, 2004·Nature Reviews. Drug Discovery·Michelle R Arkin, James A Wells
May 14, 2004·Annual Review of Biophysics and Biomolecular Structure·John SantaLucia, Donald Hicks
Sep 17, 2004·Nature·Victor Ambros
Feb 11, 2005·Chemical Reviews·Sophie Magnet, John S Blanchard
Sep 28, 2005·Nucleic Acids Research·Brian C BalesMarc M Greenberg
May 27, 2008·Nature Structural & Molecular Biology·Feng Qiao, Thomas R Cech
Sep 12, 2008·Journal of the American Chemical Society·Han ChenLarry W McLaughlin
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jonathan F ArambulaSteven C Zimmerman
Dec 3, 2009·The FEBS Journal·Anh Tuân Phan
Nov 26, 2010·Nature Chemistry·Sebastian MüllerShankar Balasubramanian
Jan 25, 2011·Organic & Biomolecular Chemistry·Harri Lönnberg
Mar 1, 2011·Methods : a Companion to Methods in Enzymology·Eduardo ParedesSubha R Das
Mar 4, 2011·Biological Procedures Online·Nathan J O'Callaghan, Michael Fenech
Mar 26, 2011·Biophysical Chemistry·Sean KelleyBesik I Kankia
Apr 2, 2011·Nature Reviews. Drug Discovery·Shankar BalasubramanianStephen Neidle
Apr 19, 2011·Journal of the American Chemical Society·Dongwon Shin, Yitzhak Tor
Jun 22, 2011·Langmuir : the ACS Journal of Surfaces and Colloids·Mingming Ma, Dennis Bong
Dec 29, 2011·Journal of the American Chemical Society·Yingying ZengDennis Bong
Dec 5, 2012·Langmuir : the ACS Journal of Surfaces and Colloids·Zhun Zhou, Dennis Bong
Jan 10, 2013·Nature Reviews. Molecular Cell Biology·Jayakrishnan Nandakumar, Thomas R Cech
Oct 12, 2013·Chembiochem : a European Journal of Chemical Biology·Eric LargyDavid M Perrin

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.