NMR analyses on N-hydroxymethylated nucleobases - implications for formaldehyde toxicity and nucleic acid demethylases

Organic & Biomolecular Chemistry
S ShishodiaRichard J Hopkinson

Abstract

Formaldehyde is produced in cells by enzyme-catalysed demethylation reactions, including those occurring on N-methylated nucleic acids. Formaldehyde reacts with nucleobases to form N-hydroxymethylated adducts that may contribute to its toxicity/carcinogenicity when added exogenously, but the chemistry of these reactions has been incompletely defined. We report NMR studies on the reactions of formaldehyde with canonical/modified nucleobases. The results reveal that hydroxymethyl hemiaminals on endocyclic nitrogens, as observed with thymidine and uridine monophosphates, are faster to form than equivalent hemiaminals on exocyclic nitrogens; however, the exocyclic adducts, as formed with adenine, guanine and cytosine, are more stable in solution. Nucleic acid demethylase (FTO)-catalysed hydroxylation of (6-methyl)adenosine results in (6-hydroxymethyl)adenosine as the major observed product; by contrast no evidence for a stable 3-hydroxymethyl adduct was accrued with FTO-catalysed oxidation of (3-methyl)thymidine. Collectively, our results imply N-hydroxymethyled adducts of nucleic acid bases, formed either by reactions with formaldehyde or via demethylase catalysis, have substantially different stabilities, with some being sufficie...Continue Reading

References

Jan 1, 1970·The Gerontologist
Aug 1, 1982·Biomedical Mass Spectrometry·H D HeckM Casanova-Schmitz
Jun 25, 1998·Experimental Gerontology·P M ServiceC A Michieli
Jun 3, 2000·Origins of Life and Evolution of the Biosphere : the Journal of the International Society for the Study of the Origin of Life·A L Weber
Sep 22, 2005·The Journal of Biological Chemistry·Dong-Hyun LeeTimothy R O'Connor
Aug 10, 2007·Proceedings of the National Academy of Sciences of the United States of America·Colleen R McNamaraChristopher M Fanger
Jul 29, 2008·Chemical Research in Toxicology·Kun LuJames A Swenberg
Feb 26, 2009·Journal of the American Chemical Society·Kun LuJames A Swenberg
Jan 23, 2010·Chembiochem : a European Journal of Chemical Biology·Richard J HopkinsonChristopher J Schofield
Aug 26, 2010·Organic & Biomolecular Chemistry·Richard J HopkinsonTimothy D W Claridge
Dec 21, 2010·Chemistry & Biology·Ivanhoe K H LeungChristopher J Schofield
Apr 1, 2011·Chemical Communications : Chem Comm·Armin ThalhammerChristopher J Schofield
Oct 18, 2011·Nature Chemical Biology·Guifang JiaChuan He
Nov 15, 2011·Nature Structural & Molecular Biology·Ivan V RosadoKetan J Patel
Oct 16, 2012·Current Opinion in Chemical Biology·Louise J WalportChristopher J Schofield
Feb 9, 2013·Trends in Biochemical Sciences·Junhui Ge, Yi-Tao Yu
Apr 4, 2013·Journal of Medicinal Chemistry·WeiShen AikChristopher J Schofield
Jun 22, 2013·Angewandte Chemie·Richard J HopkinsonChristopher J Schofield
Jul 16, 2013·Nature Genetics·Steven A RobertsDmitry A Gordenin
Nov 30, 2013·Chemical Communications : Chem Comm·Lukas LercherChristopher J Schofield
Jun 21, 2014·FEBS Letters·Eric Westhof
Sep 1, 2014·Current Opinion in Genetics & Development·Ingrun AlsethMagnar Bjørås
Oct 8, 2014·The Journal of Physical Chemistry. a·Bishnu Thapa, H Bernhard Schlegel
Jan 13, 2015·Biochimica Et Biophysica Acta·Leonie I KroezeJoop H Jansen
Jun 3, 2015·Accounts of Chemical Research·Natalia Y TretyakovaShaofei Ji
Aug 21, 2015·Nature Chemistry·Saswata KarmakarEric T Kool
Sep 6, 2015·Annals of Anatomy = Anatomischer Anzeiger : Official Organ of the Anatomische Gesellschaft·Luiza Fagundes LimaFrank Silva Bezerra
Sep 12, 2015·The Journal of Biological Chemistry·Elizabeth A HoffmanDavid T Auble
Dec 18, 2015·PloS One·Richard J HopkinsonChristopher J Schofield
May 24, 2017·Genomics, Proteomics & Bioinformatics·Pedro J Batista

❮ Previous
Next ❯

Citations

Aug 29, 2018·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Louise J Walport, Christopher J Schofield
Dec 5, 2019·Scientific Reports·Raphael ReinboldRichard J Hopkinson
Sep 30, 2020·Proceedings of the National Academy of Sciences of the United States of America·Joel D W TohChristopher J Chang
Oct 20, 2020·Biology Methods and Protocols·Yensi Flores BuesoMark Tangney
Jan 6, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Shifali Shishodia, Christopher J Schofield
Dec 11, 2020·Beilstein Journal of Organic Chemistry·Jennifer Frommer, Sabine Müller
Oct 23, 2020·Scientific Reports·Raphael ReinboldRichard J Hopkinson
Mar 31, 2021·Chemical Research in Toxicology·Jacqueline Gamboa VarelaKent S Gates
Nov 12, 2021·Journal of Medicinal Chemistry·Shifali ShishodiaChristopher J Schofield

❮ Previous
Next ❯

Methods Mentioned

BETA
NMR
1
deamination

Software Mentioned

EXSY

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

Journal of the American Chemical Society
G C LeeS I Chan
Progress in Nucleic Acid Research and Molecular Biology
M Y Feldman
© 2022 Meta ULC. All rights reserved