Nitric oxide inhibits DNA ligase activity: potential mechanisms for NO-mediated DNA damage

Carcinogenesis
M GraziewiczF Laval

Abstract

Nitric oxide-induced modifications of DNA occur either by directly altering DNA chemically through reactive nitrogen oxide species (RNOS) or indirectly by inhibiting various repair processes. DNA ligases are enzymes which rejoin single-strand breaks and are critical for DNA integrity during processes such as gene transcription and repair. The eukaryotic and T4 DNA ligases are active in the presence of ATP and act in two steps: the formation of protein-AMP intermediates, then the ligation of DNA breaks. When T4 DNA ligase was exposed to the NO generator DEA/NO (Et2N[NO(NO)]Na), a concentration- and time-dependent inhibition of these two steps, adenylylation of the protein and ligation of the substrate, was observed. This inhibition was abated by the presence of cysteine, suggesting that RNOS, rather than NO, mediated the inhibition of the ligase activity. As mammalian and T4 DNA ligases act by the same mechanism, the inhibition of DNA ligase may explain the increase in single-strand breaks reported for cells exposed to NO and provides a mechanism to increase DNA lesions without direct chemical modification of DNA by NO or RNOS.

Citations

Oct 19, 2012·Cell Biochemistry and Biophysics·Manal F Ismail, Hanaa M Mohamed
Dec 4, 2003·Free Radical Biology & Medicine·Olga SidorkinaJacques Laval
Apr 3, 2004·Free Radical Biology & Medicine·Yuan-Hung ChienKun-Yan Jan
Mar 21, 2002·The Lancet Oncology·P K Lala, C Chakraborty
Feb 23, 2007·Nature Clinical Practice. Endocrinology & Metabolism·Marinella Messina, Bruce G Robinson
Jun 13, 2012·Proceedings of the National Academy of Sciences of the United States of America·Aswin MangerichPeter C Dedon
Aug 4, 2009·The Journal of Biological Chemistry·Katherine J HughesJohn A Corbett
Mar 26, 2002·Journal of Toxicology and Environmental Health. Part a·I-Ching Ho, Te-Chang Lee
Mar 29, 2008·Antioxidants & Redox Signaling·Alexios S Strimpakos, Ricky A Sharma
Nov 19, 2008·Antioxidants & Redox Signaling·M Carmen Martínez, Ramaroson Andriantsitohaina
Mar 3, 2005·Journal of the National Cancer Institute·Elzbieta SpeinaJaroslaw T Kuśmierek
Oct 19, 2001·Journal of Clinical Gastroenterology·H J SonJ C Rhee
Oct 7, 2008·Cell Division·Gaurisankar Sa, Tanya Das
Jun 28, 2003·Proceedings of the National Academy of Sciences of the United States of America·Jeffrey M SchapiroFerric C Fang
Jan 5, 2011·Autoimmune Diseases·Jonathan WitherickKevin Kemp
Dec 8, 2015·Experimental and Therapeutic Medicine·Donatella PerroneLorenzo Lo Muzio
May 9, 2012·Mutation Research·Barbara Tudek, Elżbieta Speina
Nov 22, 2011·International Journal of Pharmaceutics·Shahana Safdar, Lakeshia J Taite
May 17, 2011·Biochimica Et Biophysica Acta·Chi-Hui TangLimin Liu
Dec 18, 2009·Mutation Research·Sabine A S LangieRoger W L Godschalk
Sep 1, 2008·Environmental Toxicology and Pharmacology·Rajarajeswaran Jayakumar, Keshavrao Sasikala
Dec 22, 2015·Coordination Chemistry Reviews·Debashree BasudharDavid A Wink
Oct 30, 2007·Free Radical Biology & Medicine·Federica ChieraMargherita Bignami
Jul 14, 2007·Molecular Aspects of Medicine·Barbara Tudek
Mar 16, 2007·The Journal of Nutritional Biochemistry·Harold E SeifriedJohn A Milner
Dec 9, 2008·The Journal of Gene Medicine·Catherine AdamsDavid G Hirst
Jan 18, 2007·The Journal of Pharmacy and Pharmacology·David Hirst, Tracy Robson
Mar 28, 2016·Critical Reviews in Oncology/hematology·Veena SomasundaramPriya Srinivas
May 29, 2004·Trends in Microbiology·Olivier TenaillonIvan Matic
Aug 16, 2005·Nitric Oxide : Biology and Chemistry·Tomohiro Sawa, Hiroshi Ohshima
Aug 6, 2005·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·R A SharmaW P Steward
Jun 25, 2015·Carcinogenesis·Sabine A S LangieAndrew R Collins
Aug 10, 2013·Free Radical Research·A MangerichG N Wogan
Feb 1, 1997·Nitric Oxide : Biology and Chemistry·D A WinkJ B Mitchell
Sep 30, 2004·Free Radical Research·Alma L RosalesMichael H L Green

❮ 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.