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Displaying 1 - 25 of 26

Possible Genetic Risks from Heat-Damaged DNA in Food

June 1, 2023
Author(s)
Yong Woong Jun, Melis Kant, Erdem Coskun, Pawel Jaruga, Miral M. Dizdar, Eric T. Kool
Consumption of foods prepared at high temperatures has been associated with numerous health risks. To date, the chief identified source of risk has been small molecules produced in trace levels by cooking and react with healthy DNA upon consumption. Here

Inhibition of human APE1 and MTH1 DNA repair proteins by dextran-coated g-Fe2O3 ultrasmall superparamagnetic iron oxide nanoparticles

February 28, 2023
Author(s)
Erdem Coskun, Pawel Jaruga, Miral M. Dizdar, Bryant C. Nelson, Neenu Singh, Leona Scanlan, Shareen Doak
Aim: To quantitatively evaluate the inhibition of human DNA repair proteins APE1 and MTH1 by dextran-coated γ-Fe2O3 ultrasmall superparamagnetic iron oxide nanoparticles (dUSPIONs). Materials & methods: Liquid chromatography–tandem mass spectrometry with

Polymorphic variant Asp239Tyr of human DNA glycosylase NTHL1 is inactive for removal of a variety of oxidatively-induced DNA base lesions from genomic DNA

July 16, 2022
Author(s)
Melis Kant, Victoria Quintana, Erdem Coskun, Pawel Jaruga, R. Stephen Lloyd, Joann Sweasy, Miral M. Dizdar
Base excision repair is the major pathway for the repair of oxidatively-induced DNA damage with DNA glycosylases removing modified DNA bases in the first step. Among them, human NTHL1 is specific for excision of several pyrimidine- and purine-derived

Inhibition by Tetrahydroquinoline Sulfonamide Derivatives of the Activity of Human 8-Oxoguanine DNA Glycosylase (OGG1) for Several Products of Oxidatively-induced DNA Base Lesions

December 17, 2021
Author(s)
Miral M. Dizdar, Melis Kant, Pawel Jaruga, Erdem Coskun, Yu-Ki Tahara, R. S. Lloyd, Eric T. Kool
DNA glycosylases involved in the first step of the base excision repair pathway of DNA repair are promising targets in cancer therapy. There is evidence that reduction of their activities may enhance cell killing in malignant tumors. Recently, two

DNA glycosylase deficiency leads to decreased severity of lupus in the Polb-Y265C mouse model

June 24, 2021
Author(s)
Sesha Paluri, Matthew Burak, Alireza Senenjani, Kelly Carufe, Kaylin Clairmont, Isabel Alvarado-Cruz, Rithy Meas, Michael Kashgarian, Caroline Zeiss, Stephen Maher, Alfred Bothwell, Erdem Coskun, Melis Kant, Pawel Jaruga, Miral M. Dizdar, R S. Lloyd, Joann B. Sweasy
The Polb gene encodes DNA polymerase beta (Pol β), a DNA polymerase that functions in base excision repair (BER) and microhomology-mediated end-joining. The Pol β-Y265C protein exhibits low catalytic activity and fidelity, and is also deficient in

Ne-22 Ion-Beam Radiation Damage to DNA: From Initial Free Radical Formation to Resulting DNA-Base Damage

June 14, 2021
Author(s)
Melis Kant, Pawel Jaruga, Erdem Coskun, Samuel Ward, Alexander Stark, Thomas Baumann, David Becker, Amitava Adhikary, Michael Sevilla, Miral M. Dizdar
We report on the physicochemical processes and the products of DNA damage involved in Ne-22 ion-beam radiation of hydrated (12±3 H2O/nucleotide) salmon sperm DNA at 77 K. Free radicals trapped at 77 K were identified using electron spin resonance (ESR)

Chapter 4: Oxidatively induced DNA damage: Mechanisms and measurement

November 20, 2020
Author(s)
Miral M. Dizdar, Erdem Coskun, Gamze Tuna, Melis Kant, Pawel Jaruga
Oxidatively induced damage to DNA occurs in living organisms by endogenously or exogenously generated reactive species including free radicals. Mounting evidence suggests that this type of DNA damage plays an important role in the etiology of numerous

Expression of a germline variant in the N-terminal domain of the human DNA glycosylase NTHL1 induces cellular transformation without impairing enzymatic function or substrate specificity

June 16, 2020
Author(s)
Carolyn G. Marsden, Pawel Jaruga, Erdem Coskun, Robyn L. Maher, David S. Pederson, Miral M. Dizdar, Joann B. Sweasy
Oxidatively-induced DNA damage, widely accepted as a key player in the onset of cancer, is predominantly repaired by base excision repair (BER). BER is initiated by DNA glycosylases, which locate and remove damaged bases from DNA. NTHL1 is a bifunctional

Ion-beam radiation damage to DNA by investigation of free radical formation and base damage

March 1, 2020
Author(s)
Melis Kant, Pawel Jaruga, Erdem Coskun, Samuel Ward, Alexander Stark, David Becker, Amitav Adhikary, Michael Sevilla, Miral M. Dizdar
This work investigated the physicochemical processes and DNA base products involved in Ne-22 ion- beam (ca. 1.4 GeV) radiation damage to hydrated (12 waters/nucleotide) highly polymerized salmon sperm DNA. For this purpose, approximately 12 small (ca. 10

Measurement of PARP1 in human tissues by liquid chromatography tandem mass spectrometry

March 1, 2020
Author(s)
Erdem Coskun, Gamze Tuna, Pawel Jaruga, Alessandro Tona, Onur Erdem, Miral M. Dizdar
Poly(ADP ribose) polymerase 1 (PARP1) is a multifunctional DNA repair protein of the base excision repair pathway and plays a major role in the repair of DNA strand breaks and in replication and transcriptional regulation among other functions. Mounting

Recognition of DNA adducts by edited and unedited forms of DNA glycosylase NEIL1

November 2, 2019
Author(s)
Irina G. Minko, Vladimir Vartanian, Naoto Tozaki, Erdem Coskun, Sanem Hosbas Coskun, Pawel Jaruga, J Yeo, M.P. Stone, M Egli, Miral M. Dizdar, Amanda K. McCullough, R S. Lloyd
Pre-mRNA encoding human NEIL1 undergoes editing by adenosine deaminase ADAR1 that converts a single adenosine to inosine, and this conversion results in an amino acid change of lysine 242 to arginine. Previous investigations of the catalytic efficiencies

Measurement of Oxidatively Induced DNA Damage in Caenorhabditis elegans with High-Salt DNA Extraction and Isotope-Dilution Mass Spectrometry

August 27, 2019
Author(s)
Leona D. Scanlan, Pawel Jaruga, Sanem Hosbas Coskun, Christopher Sims, Shannon Hanna, Jamie L. Almeida, David N. Catoe, Bryant C. Nelson, Miral M. Dizdar, Erdem Coskun
Caenorhabditis elegans (C. elegans) is used as a medical and systems toxicity model organism for environmental and developmental assays that include high-throughput methods and genetic studies. However, little is known about background levels of

Characterization of Rare NEIL1 Variants Found in East Asian Populations

May 3, 2019
Author(s)
Irina G. Minko, Vladimir Vartanian, Naoto Tozaki, Oskar Linde, Pawel Jaruga, Sanem Hosbas Coskun, Erdem Coskun, Chunfeng Qu, Huan He, Taoyang Chen, Qianqian Song, Yuchen Jiao, Michael Stone, Martin Egli, Miral M. Dizdar, Amanda K. McCullough, R S. Lloyd
The combination of chronic dietary exposure to the fungal toxin, aflatoxin B1 (AFB1), and hepatitis B viral (HBV) infection is associated with an increased risk for early onset hepatocellular carcinomas (HCCs). An in-depth knowledge of the mechanisms

Identification and quantification of DNA repair protein poly(ADP ribose) polymerase 1 (PARP1) in human tissues and cultured cells by liquid chromatography/isotope-dilution tandem mass spectrometry

March 1, 2019
Author(s)
Erdem Coskun, Gamze Tuna, Pawel Jaruga, Alessandro Tona, Onur Erdem, M Miral Dizdar
Poly(ADP ribose) polymerase 1 (PARP1) is a multifunctional DNA repair protein of the base excision repair pathway and plays a major role in the repair of DNA strand breaks and in replication and transcriptional regulation among other functions. Mounting

Aflatoxin-guanine DNA Adducts and Oxidatively-induced DNA Damage in Aflatoxin-treated Mice in vivo as Measured by Liquid Chromatography-Tandem Mass Spectrometry with Isotope-dilution

December 11, 2018
Author(s)
Erdem Coskun, Pawel Jaruga, Vladimir Vartanian, Onur Erdem, Patricia Egner, John D. Groopman, R. S. Lloyd, Miral M. Dizdar
Dietary exposure to aflatoxin (AFB1) is a significant reason for the incidence of hepatocellular carcinomas globally. AFB1-exposure leads to the formation of AFB1-N7-guanine (AFB1-N7-Gua) and two diastereomers of 8,9-dihydro-8-(2,6-diamino-4-oxo-3,4

Identification and Quantification of Aflatoxin Guanine and FapyGuanine Adducts in Mouse Liver invivo by LC-MS/MS Isotope Dilution

March 11, 2018
Author(s)
Erdem Coskun, Vladimir Vartanian, Irina G. Minko, Onur Erdem, Pawel Jaruga, Patricia Egner, John D. Groopman
Dietary exposures to aflatoxin contaminated food is one of the major contributions to human hepatocellular carcinomas (HCCs) which accounts for over 700.000 deaths per year, especially in highly populated developing and underdeveloped countries. Aflatoxin

Small molecule inhibitors of DNA glycosylases as potential drugs in cancer therapy

August 31, 2017
Author(s)
M Miral Dizdar, Aaron C. Jacobs, Nathan Donley, Marcus J. Calkins, Ajit Jadhav, Dorjbal Dorjsuren, David Maloney, Anton Simeonov, Pawel Jaruga, Erdem Coskun, Amanda K. McCullough, R. S. Lloyd
Statement of the Problem: Most chemotherapeutic agents kill cancer cells by damaging DNA. Cancer cells overexpress DNA repair proteins and thus increase DNA repair capacity that can cause resistance to therapy by removing DNA lesions before they become

Exposure to Engineered Nanomaterials: Impact on DNA Repair Pathways

July 13, 2017
Author(s)
Neenu Singh, Bryant C. Nelson, Leona D. Scanlan, Erdem Coskun, Pawel Jaruga, Shareen Doak
Some engineered nanomaterials (ENMs) may have the potential to cause damage to the genetic material in living systems. The mechanistic machinery functioning at the cellular/molecular level, in the form of DNA repair processes, has evolved to help

Enhancing the Efficacy of Cancer Therapy: Use of Small Molecule Inhibitors of DNA Glycosylases as Potential Drugs

March 12, 2017
Author(s)
Erdem Coskun, Aaron C. Jacobs, Nathan Donley, Marcus J. Calkins, Dorjbal Dorjsuren, David Maloney, Anton Simeonov, Pawel Jaruga, Amanda K. McCullough, M Miral Dizdar, R. S. Lloyd
Chemotherapy aims to destroy cancer cells by damaging their DNA. However, the overexpression of DNA repair proteins in cancer cells causes the removal of DNA lesions before they become toxic and thus leads to an increased DNA repair capacity resulting in

Repair of Oxidatively Induced DNA Damage by DNA Glycosylases

February 16, 2017
Author(s)
M Miral Dizdar, Erdem Coskun, Pawel Jaruga
Endogenous and exogenous reactive species cause oxidatively induced DNA damage in living organisms by a variety of mechanisms. As a result, a plethora of mutagenic and/or cytotoxic products are formed in cellular DNA. This type of DNA damage is repaired by

Combined Effects of High-Dose Bisphenol A and Oxidizing Agent (KBrO3) on Cellular Microenvironment, Gene Expression, and Chromatin Structure of Ku70-deficient Mouse Embryonic Fibroblasts

April 15, 2016
Author(s)
Erdem Coskun, Pawel Jaruga, Miral M. Dizdar, Natalie Gassman, Samuel Wilson
Background: Exposure to the environmental endocrine disrupting chemical bisphenol A (BPA) has been reported to alter global gene expression, induce epigenetic modifications, and interfere with the complex regulatory networks of cells. In addition to these

Extreme expression of DNA repair protein apurinic/apyrimi-dinic endonuclease I (APE1) in human breast cancer as measured by liquid-chromatography isotope-dilution tandem mass spectrometry

September 15, 2015
Author(s)
Erdem Coskun, Pawel Jaruga, Prasad T. Reddy, Miral M. Dizdar
Apurinic/apyrimidinic endonuclease 1 (APE1) is a DNA re-pair protein and plays other important roles. Increased lev-els of APE1 in cancer have been reported. However, avail-able methods to measure APE1 levels are indirect and not quantitative. We