Mammalian DNA repair methyltransferases shield O4MeT from nucleotide excision repair

Carcinogenesis
L SamsonL J Rasmussen

Abstract

O6-Methylguanine (O6MeG) and O4-methylthymine (O4MeT) are potentially mutagenic DNA lesions that cause G:C-->A:T and A:T-->G:C transition mutations by mispairing during DNA replication, and the repair of O6MeG and O4MeT by DNA repair methyltransferases (MTases) is therefore expected to prevent methylation-induced transitions. The efficiency of O6MeG and O4MeT repair by different MTases can vary by several hundred-fold and the aim of this study was to establish the biological consequences of such differences in the efficiency of repair. The ability of three microbial and two mammalian MTases to prevent methylation-induced G:C-->A:T and A:T-->G:C transitions is taken as a measure of their ability to repair O6MeG and O4MeT in vivo respectively. All five MTases give complete protection against G:C-->A:T transitions. However, while the microbial MTases give complete protection against A:T-->G:C transitions, the mammalian MTases actually sensitize cells to A:T-->G:C transitions. We hypothesize that the mammalian MTases bind O4MeT lesions in vivo but that, because they are extremely slow at subsequent methyl transfer, binding shields O4MeT from repair by the nucleotide excision repair pathway. Results are presented to support this hyp...Continue Reading

Citations

Dec 3, 2008·Chemico-biological Interactions·Claus DeslerLene Juel Rasmussen
Nov 6, 2003·Toxicology·Markus ChristmannBernd Kaina
Apr 18, 2000·Mutation Research·A E Pegg
Aug 21, 2008·Chemical Research in Toxicology·Aley G KalapilaAnthony E Pegg
Dec 23, 2009·The Journal of Biological Chemistry·Qingming FangAnthony E Pegg
Oct 31, 2009·Carcinogenesis·Nidhi ShrivastavJohn M Essigmann
Oct 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·S S HechtS E Murphy
Dec 18, 2001·Environmental and Molecular Mutagenesis·S Kanugula, A E Pegg
Mar 14, 2002·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Geoffrey P Margison, Mauro F Santibáñez-Koref
May 8, 2007·DNA Repair·Anthony E PeggNatalia A Loktionova
Aug 5, 2014·Chembiochem : a European Journal of Chemical Biology·Francis P McManus, Christopher J Wilds
Sep 24, 2004·DNA Repair·Finn DrabløsHans E Krokan
Nov 16, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Nadia M SchoonhovenChristopher J Wilds
Aug 2, 2002·The Journal of Biological Chemistry·Liping LiuF Peter Guengerich
May 3, 2003·Nature Reviews. Molecular Cell Biology·Susan D Cline, Philip C Hanawalt
Jun 7, 2019·The Journal of Biological Chemistry·Hua DuYinsheng Wang
Dec 17, 2014·Current Protocols in Nucleic Acid Chemistry·Derek K O'Flaherty, F Peter Guengerich
Jan 13, 2021·Critical Reviews in Biochemistry and Molecular Biology·Ning TsaoNima Mosammaparast

❮ 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.