Article
Genetics & Heredity
Andrea Huskova, Barbora Landova, Evzen Boura, Jan Silhan
Summary: This study investigates the formation of DNA interstrand crosslinks (ICLs) derived from abasic (Ap) sites. The findings reveal that AT-rich regions in the DNA sequence context lead to higher rates of Ap-ICL formation.
Article
Chemistry, Multidisciplinary
Saosan Binth Md. Amin, Tanhaul Islam, Nathan E. Price, Amanda Wallace, Xu Guo, Anuoluwapo Gomina, Marjan Heidari, Kevin M. Johnson, Calvin D. Lewis, Zhiyu Yang, Kent S. Gates
Summary: The study examined the effects of reaction conditions, additives, and local sequences on the formation and stability of interstrand cross-links (ICLs) in duplex DNA. Results showed that ICLs can occur in a wide variety of physiological conditions and were inhibited to some extent by specific compounds.
Article
Multidisciplinary Sciences
Aaron L. Rozelle, Young Cheun, Caroline K. Vilas, Myong-Chul Koag, Seongmin Lee
Summary: Oxidative damage to DNA generates 7,8-dihydro-8-oxoguanine and 7,8-dihydro-8-oxoadenine, with the latter forming DNA interstrand crosslinks upon secondary oxidation induced by reactive halogen species, one-electron oxidants, and the myeloperoxidase/H2O2/Cl- system. This highlights the potential biological implications of these lesions and the mechanism of ICL formation by oxidized nucleobases, particularly 7,8-dihydro-8-oxoadenine.
NATURE COMMUNICATIONS
(2021)
Review
Genetics & Heredity
Kurt Housh, Jay S. Jha, Tuhin Haldar, Saosan Binth Md Amin, Tanhaul Islam, Amanda Wallace, Anuoluwapo Gomina, Xu Guo, Christopher Nel, Jesse W. Wyatt, Kent S. Gates
Summary: Genome integrity is crucial for life, and DNA repair systems have evolved to remove unavoidable DNA lesions. Many life forms have the ability to remove DNA interstrand cross-links (ICLs), but the identity of the naturally-occurring substances that drove the evolution and retention of these DNA repair systems is still uncertain. This review discusses various chemical processes through which endogenous ICLs may be introduced into cellular DNA, involving DNA degradation processes, reactions with low molecular weight aldehyde metabolites, and reactions with DNA radicals generated by oxidation.
Article
Chemistry, Medicinal
Jacqueline Gamboa Varela, Luke E. Pierce, Xu Guo, Nathan E. Price, Kevin M. Johnson, Zhiyu Yang, Yinsheng Wang, Kent S. Gates
Summary: Interstrand cross-link formation in duplex DNA can be pH-dependent and stable, with cytosine playing a role in forming cross-links with an AP site. Different nucleobase cross-links can coexist in dynamic equilibrium in some sequences, and the presence of a reducing agent can shift the equilibrium towards the formation of specific cross-links.
CHEMICAL RESEARCH IN TOXICOLOGY
(2021)
Article
Chemistry, Physical
Ye-Guang Fang, Danillo Valverde, Sebastian Mai, Sylvio Canuto, Antonio Carlos Borin, Ganglong Cui, Leticia Gonzalez
Summary: The excited-state properties and relaxation mechanisms of 6-selenoguanine after light irradiation in water and DNA are investigated using a QM/MM approach with MS-CASPT2 method, revealing similar behaviors but faster S-2 -> S-1 internal conversion in DNA due to a steeper potential energy surface.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
Article
Chemistry, Analytical
Francesca Ripanti, Claudia Fasolato, Flavia Mazzarda, Simonetta Palleschi, Marina Ceccarini, Chunchun Li, Margherita Bignami, Enrico Bodo, Steven E. J. Bell, Filomena Mazzei, Paolo Postorino
Summary: This study introduces a novel method for the identification, detection, and quantification of oxidized nucleotides using micro-Raman spectroscopy and ab initio calculations. The Raman signature in the terahertz spectral range contains information on the assembly of guanine in tetrads, allowing for improved detection of oxidative damage. Furthermore, advanced spectroscopic methods combined with surface-enhanced Raman scattering on superhydrophobic substrates enable analysis of samples at very low concentrations in small volumes.
ANALYTICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Julio C. Gonzalez-Olvera, Absalom Zamorano-Carrillo, Gerardo Arreola-Jardon, Reynaldo C. Pless
Summary: This study investigated the effect of vicinal molecular groups on the intrinsic acidity of a central guanine residue in DNA using the FMO method. The acidity of guanine was found to decrease with increasing oligonucleotide length, which was attributed to the electrostatic influence of negative charges on the backbone. Furthermore, the electric-field effect was demonstrated through the displacement of a test hydronium ion, showing agreement with experimental results. These findings have implications for biophysical applications involving the induction of negative charges at specific positions in DNA.
JOURNAL OF MOLECULAR MODELING
(2022)
Article
Biochemistry & Molecular Biology
Takao Yamaguchi, Naohiro Horie, Hiroshi Aoyama, Shinji Kumagai, Satoshi Obika
Summary: Antisense oligonucleotides (ASOs) have emerged as a promising class of drugs for the treatment of various diseases. In order to improve their stability and duplex-forming ability, modified nucleic acids have been developed by modulating sugar conformation and incorporating various substituents. This study introduces the incorporation of an N-tert-butylguanidinium group at the 2',4'-bridging structure, which greatly enhances duplex-forming ability by interacting with the minor groove. Hydrophobic substituents fitting the grooves of duplexes also show potential in increasing duplex-forming ability.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Tingyu Wen, Kun Yang, Marc M. Greenberg
Summary: Positively charged N-terminal histone tails play important roles in maintaining the nucleosome structure and function. They modulate the local ionic environment within a nucleosome core particle (NCP) and impact DNA damage and other processes. By studying NCPs with wild-type or mutated histones and a fluorescent probe, it has been shown that interaction with positively charged N-terminal tails increases the local ionic strength near nucleosomal DNA.
Article
Genetics & Heredity
Niketa Bhawsinghka, Adam Burkholder, Roel M. Schaaper
Summary: Mutation is a natural process that occurs in all organisms, including bacteria. While the mutation rates in bacteria are usually low, they can be significantly increased under stress or in harmful environments. Studying mutation frequencies and types can provide insights into the mechanisms and pathways involved in mutations. The recent development of Duplex Sequencing allows for direct detection of mutations, providing a more accurate approach.
Article
Chemistry, Medicinal
Arnold S. Groehler, Asema Maratova, Nhat Mai Dao, Anuar Mahkmut, Orlando D. Scharer
Summary: Cisplatin (CP) is an effective antitumor drug used to treat various solid tumors. This study developed ultraperformance liquid chromatography-selective ion monitoring (UPLC-SIM) assays to accurately quantify different types of intrastrand cross-links formed by CP. The results showed that 1,2-GG-intrastrand cross-links were the most abundant and formed at a faster rate. Additionally, the repair kinetics of intrastrand cross-links were investigated in wild-type and nucleotide excision repair (NER)-deficient cells, demonstrating a slower decrease in cross-links in wild-type cells and no direct repair in NER-deficient cells.
CHEMICAL RESEARCH IN TOXICOLOGY
(2023)
Article
Chemistry, Medicinal
Ashis K. Basu, John M. Essigmann
Summary: DNA damage can lead to a diverse spectrum of mutations, making the understanding of mutagenesis process crucial for human health preservation. Chemical or physical agents causing cancer often leave behind mutational fingerprints, which can be used to uncover the molecular events that led to the disease. The field of single-lesion mutagenesis has witnessed significant growth in the past three decades.
CHEMICAL RESEARCH IN TOXICOLOGY
(2022)
Article
Chemistry, Organic
Ujjal Sarkar, Roman Hillebrand, Kevin M. Johnson, Andrea H. Cummings, Ngoc Linh Phung, Anuruddha Rajapakse, Haiying Zhou, Jordan R. Willis, Charles L. Barnes, Kent S. Gates
JOURNAL OF HETEROCYCLIC CHEMISTRY
(2017)
Article
Biochemistry & Molecular Biology
Maryam Imani Nejad, Kevin M. Johnson, Nathan E. Price, Kent S. Gates
Article
Biochemistry & Molecular Biology
Valerie M. Kramlinger, Leslie D. Nagy, Rina Fujiwara, Kevin M. Johnson, Thanh T. N. Phan, Yi Xiao, Jennifer M. Enright, Matthew B. Toomey, Joseph C. Corbo, Frederick Peter Guengerich
Article
Biochemistry & Molecular Biology
Jin Wang, Hongping Dong, Yok Hian Chionh, Megan E. McBee, Sasilada Sirirungruang, Richard P. Cunningham, Pei-Yong Shi, Peter C. Dedon
NUCLEIC ACIDS RESEARCH
(2016)
Article
Chemistry, Applied
Mohammed N. A. Khalil, Mostafa I. Fekry, Mohamed A. Farag
Article
Chemistry, Medicinal
Mohamed A. Farag, Mostafa I. Fekry, Montasser A. Al-Hammady, Mohamed N. Khalil, Hesham R. El-Seedi, Achim Meyer, Andrea Porzel, Hildegard Westphal, Ludger A. Wessjohann
Article
Toxicology
Jianbo Zhang, Michael T. Empl, Clarissa Schwab, Mostafa I. Fekry, Christina Engels, Mirjam Schneider, Christophe Lacroix, Pablo Steinberg, Shana J. Sturla
TOXICOLOGICAL SCIENCES
(2017)
Article
Chemistry, Organic
Xiulong Shen, Charles H. Laber, Ujjal Sarkar, Fabio Galazzi, Kevin M. Johnson, Nathaniel G. Mahieu, Roman Hillebrand, Tarra Fuchs-Knotts, Charles L. Barnes, Gary A. Baker, Kent S. Gates
JOURNAL OF ORGANIC CHEMISTRY
(2018)
Article
Biochemistry & Molecular Biology
Andria R. Robinson, Matthew J. Yousefzadeh, Tania A. Rozgaja, Jin Wang, Xuesen Li, Jeremy S. Tilstra, Chelsea H. Feldman, Siobhan Q. Gregg, Caroline H. Johnsong, Erin M. Skoda, Marie-Celine Frantz, Harris Bell-Temin, Hannah Pope-Varsalona, Aditi U. Gurkar, Luigi A. Nasto, Rena A. S. Robinson, Heike Fuhrmann-Stroissnigg, Jolanta Czerwinska, Sara J. McGowan, Nadiezhda Cantu-Medellin, Jamie B. Harris, Salony Maniar, Mark A. Ross, Christy E. Trussoni, Nicholas F. LaRusso, Eugenia Cifuentes-Pagano, Patrick J. Pagano, Barbara Tudek, Nam V. Vo, Lora H. Rigatti, Patricia L. Opresko, Donna B. Stolz, Simon C. Watkins, Christin E. Burd, Claudette M. St Croix, Gary Siuzdak, Nathan A. Yates, Paul D. Robbins, Yinsheng Wang, Peter Wipf, Eric E. Kelley, Laura J. Niedernhofer
Article
Multidisciplinary Sciences
Mostafa I. Fekry, Shahira M. Ezzat, Maha M. Salama, Ohoud Y. Alshehri, Ahmed M. Al-Abd
SCIENTIFIC REPORTS
(2019)
Article
Pharmacology & Pharmacy
Mostafa Fekry, Yi Xiao, Jeannette Zinggeler Berg, F. Peter Guengerich
DRUG METABOLISM AND DISPOSITION
(2019)
Article
Biochemistry & Molecular Biology
Jin Wang, Bing Liang Alvin Chew, Yong Lai, Hongping Dong, Luang Xu, Seetharamsingh Balamkundu, Weiling Maggie Cai, Liang Cui, Chuan Fa Liu, Xin-Yuan Fu, Zhenguo Lin, Pei-Yong Shi, Timothy K. Lu, Dahai Luo, Samie R. Jaffrey, Peter C. Dedon
NUCLEIC ACIDS RESEARCH
(2019)
Article
Neurosciences
Chang Liu, Rebecca Reese, Simon Vu, Lionel Rouge, Shannon D. Shields, Satoko Kakiuchi-Kiyota, Huifen Chen, Kevin Johnson, Yu Patrick Shi, Tania Chernov-Rogan, Demi Maria Zabala Greiner, Pawan Bir Kohli, David Hackos, Bobby Brillantes, Christine Tam, Tianbo Li, Jianyong Wang, Brian Safina, Steve Magnuson, Matthew Volgraf, Jian Payandeh, Jie Zheng, Alexis Rohou, Jun Chen
Summary: A non-covalent agonist, GNE551, has been discovered to activate TRPA1 ion channel differently from covalent agonists, inducing persistent pain. The cryo-EM structure of the TRPA1-GNE551 complex reveals a distinct binding pocket and ligand-interaction mechanism. This biased agonism of TRPA1 has important implications for the development of effective drugs tailored to different disease etiologies.
Review
Pharmacology & Pharmacy
S. Cyrus Khojasteh, Upendra A. Argikar, Sungjoon Cho, Rachel Crouch, Carley J. S. Heck, Kevin M. Johnson, Amit S. Kalgutkar, Lloyd King, Hlaing (Holly) Maw, Herana Kamal Seneviratne, Shuai Wang, Cong Wei, Donglu Zhang, Klarissa D. Jackson
Summary: This review provides a comprehensive overview of the recent advancements in the field of biotransformation, including new modalities, drug discovery, and drug development.
DRUG METABOLISM REVIEWS
(2022)
Article
Biochemical Research Methods
Jin Wang, Bing Liang Alvin Chew, Yong Lai, Hongping Dong, Luang Xu, Yu Liu, Xin-Yuan Fu, Zhenguo Lin, Pei-Yong Shi, Timothy K. Lu, Dahai Luo, Samie R. Jaffrey, Peter C. Dedon
Summary: Chemical modifications of transcripts with a 5' cap are important for RNA metabolism. CapQuant is a mass spectrometry-based technique that accurately and sensitively quantifies the cap epitranscriptome. It can analyze various types of RNA and provides superior specificity, sensitivity, and accuracy compared to other methods. CapQuant's ability to reveal the landscape of RNA caps and the distribution of transcription start sites makes it valuable for studying RNA biology.