Insight into the sequence-specific elements leading to increased DNA bending and ligase-mediated circularization propensity by antitumor trabectedin.

Journal of Computer-aided Molecular Design
Alberto Mills, Federico Gago

Abstract

DNA curvature is the result of a combination of both intrinsic features of the double helix and external distortions introduced by the environment and the binding of proteins or drugs. The propensity of certain double-stranded DNA (dsDNA) sequences to bend is essential in crucial biological processes, such as replication and transcription, in which proteins are known to either recognize noncanonical DNA conformations or promote their formation upon DNA binding. Trabectedin (Yondelis®) is a clinically used antitumor drug which, following covalent bond formation with the 2-amino group of guanine, induces DNA curvature and enhances the circularization ratio, upon DNA ligation, of several dsDNA constructs but not others. By means of unrestrained molecular dynamics simulations using explicitly solvated all-atom models, we rationalize these experimental findings in structural terms and shed light on the crucial, albeit possibly underappreciated, role played by T4 DNA ligase in stabilizing a bent DNA conformation prior to cyclization. Taken together, our results expand our current understanding on how DNA shape modification by trabectedin may affect both the sequence-specific recognition by transcription factors to promoter sites and ...Continue Reading

References

Aug 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·D ShoreR L Baldwin
Jul 20, 1999·Journal of Medicinal Chemistry·M Zewail-Foote, L H Hurley
Jun 20, 2000·Biochemistry·A A Salzberg, P C Dedon
Feb 13, 2003·Current Opinion in Structural Biology·Kazuhiro OgataTahir Tahirov
Apr 12, 2003·Acta Crystallographica. Section C, Crystal Structure Communications·C Ignacio Sainz-DiazJuanma Garcia-Ruiz
Nov 7, 2007·Nucleic Acids Research·Sarah A HarrisTanniemola B Liverpool
Oct 18, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Gregory J AuneYves Pommier
Feb 5, 2009·Molecular Cancer Therapeutics·Claudia ForniRoberto Mantovani
Jun 11, 2009·Quarterly Reviews of Biophysics·Tali E Haran, Udayan Mohanty
Jul 25, 2009·Nucleic Acids Research·R LaveryK Zakrzewska
Dec 10, 2009·Methods in Molecular Biology·Hao Wang, Charles A Laughton
Jan 30, 2013·Biochemical Society Transactions·Andreas Gietl, Dina Grohmann
Nov 12, 2013·Oncogene·S Di GiandomenicoM D'Incalci
Mar 25, 2014·Journal of Chemical Theory and Computation·Pengfei Li, Kenneth M Merz
Apr 7, 2015·Cell·Namiko AbeRichard S Mann
Nov 17, 2015·Nature Methods·Ivan IvaniModesto Orozco
Nov 18, 2015·Journal of Chemical Theory and Computation·James A MaierCarlos Simmerling
Jul 9, 2013·Journal of Chemical Theory and Computation·Daniel R Roe, Thomas E Cheatham
Dec 17, 2015·Cancer Chemotherapy and Pharmacology·Annette K LarsenMaurizio D'Incalci
Dec 3, 2016·Nucleic Acids Research·Arka ChakrabortyMaria Solà
Feb 24, 2018·Molecular Systems Biology·H Tomas RubeHarmen J Bussemaker
May 23, 2018·Nucleic Acids Research·Andrew WaterhouseTorsten Schwede
Jul 22, 2019·Journal of Molecular Biology·Federica BattistiniModesto Orozco
May 5, 2020·Nucleic Acids Research·Adele Williamson, Hanna-Kirsti S Leiros
Jun 3, 2020·Nature Medicine·Paulina J Dziubańska-KusibabThomas F Meyer
Nov 19, 2020·Biochemistry·Samuel Lara-GonzalezCatherine L Lawson
Dec 18, 2020·Nature·Aakash BasuTaekjip Ha

❮ Previous
Next ❯

Citations

Jul 24, 2021·Organic & Biomolecular Chemistry·Alberto Mills, Federico Gago

❮ 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.

Related Papers

British Journal of Clinical Pharmacology
Eline A Dubois, Adam F Cohen
The Oncologist
Meredith K ChukElizabeth Fox
Cancer Chemotherapy and Pharmacology
Annette K LarsenMaurizio D'Incalci
The American Journal of the Medical Sciences
J E Gee, D M Miller
© 2021 Meta ULC. All rights reserved