Article
Biochemistry & Molecular Biology
Haritha Asha, Petr Stadlbauer, Lara Martinez-Fernandez, Pavel Banas, Jiri Sponer, Roberto Improta, Luciana Esposito
Summary: The study investigates the structural behavior of a quadruplex helix sequence in human telomeres when one of the G bases is ionized to G(center dot+). It is found that the position of G(center dot+) influences structural rearrangements, electrostatic repulsion, and solvent exposure, providing new insights into guanine reactions. The research suggests structural determinants of reactivity and implications for understanding reactivity in other G-quadruplex topologies.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Chemistry, Multidisciplinary
Ismail A. Elhaty
Summary: The study found that the quinazoline derivative GW2974 has a strong affinity for human telomeric G-quadruplex, and can inhibit telomerase enzyme activity by altering the stability of G-quadruplex DNA.
Article
Chemistry, Organic
Sarmistha Pal, Khushnood Fatma, Velayutham Ravichandiran, Jyotirmayee Dash
Summary: The triazolyl dibenzo[a,c]phenazine derivatives synthesized in this study were found to bind to G-quadruplexes and reduce telomerase activity in cancer cells.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Cell Biology
Shalu Sharma, Ananda Kishore Mukherjee, Shuvra Shekhar Roy, Sulochana Bagri, Silje Lier, Meenakshi Verma, Antara Sengupta, Manish Kumar, Gaute Nesse, Deo Prakash Pandey, Shantanu Chowdhury
Summary: The study reveals that the telomere-repeat-binding-factor TRF2 binds to G-quadruplexes in the hTERT promoter, leading to H3K27 trimethylation and repression of hTERT in both cancer and normal cells. Two highly recurrent hTERT promoter mutations found in many cancers disrupt G-quadruplexes, resulting in loss of TRF2 binding.
Article
Chemistry, Analytical
Yujing Zhang, Likang Sun, Xiaoxuan Xiang, Ying Bao, Xinhua Guo
Summary: The use of surface-enhanced Raman spectroscopy (SERS) can identify the structural details of DNA G-quadruplexes, especially the number of adenine (A) bases on the G-quartet. This method is simple, fast, low cost, and sensitive, providing specific structural details in aqueous solution with widespread applications.
Article
Chemistry, Multidisciplinary
Jeremie Mitteaux, Pauline Lejault, Filip Wojciechowski, Alexandra Joubert, Julien Boudon, Nicolas Desbois, Claude P. Gros, Robert H. E. Hudson, Jean-Baptiste Boule, Anton Granzhan, David Monchaud
Summary: This article reports on efforts to develop in vitro assays to reliably identify molecules that can destabilize G4s. The workflow includes a newly designed G4-unfold assay, adapted from the G4-helicase assay with Pif1, as well as biophysical and biochemical techniques traditionally used to study G4/ligand interactions, and a qPCR stop assay adapted from a Taq-based protocol to identify G4s in genomic DNA. This multipronged approach leads to the characterization of a phenylpyrrolocytosine (PhpC)-based G-clamp analog as a prototype of a G4-disrupting small molecule.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Medicinal
Domen Oblak, Hadzi, Crtomir Podlipnik, Jurij Lah
Summary: The authors investigated the (un)folding and binding process of a human telomeric fragment with ligands through calorimetry and spectroscopy. The results showed that the presence of specific ligands can alter the topology of G-quadruplex nucleic acids. By analyzing thermodynamic parameters and conducting molecular modeling, the driving forces behind the topological transformations were clarified.
Article
Biochemistry & Molecular Biology
Taniya Sharma, Nikita Kundu, Sarvpreet Kaur, Vibha Tandon, J. Shankaraswamy, Sarika Saxena
Summary: This study provides evidence of human telomeric G4 destabilization upon peptide binding in dilute and cell-mimicking conditions, suggesting the potential therapeutic targets for diseases with over-representation of G4 motifs.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Valentina Pirota, Chiara Platella, Domenica Musumeci, Alessandra Benassi, Jussara Amato, Bruno Pagano, Giorgio Colombo, Mauro Freccero, Filippo Doria, Daniela Montesarchio
Summary: NDI-5 has shown promising potential as a ligand for multimeric G4 structures, selectively targeting them over duplex DNA. Experimental analyses including CD, gel electrophoresis, ITC, and fluorescence spectroscopy suggest that NDI-5 effectively binds and stabilizes tel46 G4, favoring a hybrid folding in K+-containing buffer.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Mina Maddah, Leila Karami
Summary: This study investigates the binding of two ligands to the G-quadruplex through Molecular Dynamics simulation, showing that the ligands can significantly enhance the stability and rigidity of the G-quadruplex. The charged ligand has a greater impact on stability, while the uncharged ligand focuses more on van der Waals interaction. Energy decomposition and radial distribution function analysis provide insights into the binding mechanism and conformational changes.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Review
Cell Biology
Lucille Ferret, Karla Alvarez-Valadez, Jennifer Riviere, Alexandra Muller, Natalia Bohalova, Luo Yu, Lionel Guittat, Vaclav Brazda, Guido Kroemer, Jean-Louis Mergny, Mojgan Djavaheri-Mergny
Summary: Guanine-quadruplex structures (G4) are formed by guanine-rich DNA and RNA sequences and control gene expression mechanisms. G4 ligands have been developed for potential therapeutic applications in human diseases. Recent evidence suggests that G4 ligands may target cellular components such as lysosomes and mitochondria.
Article
Biochemistry & Molecular Biology
Nikita Kundu, Taniya Sharma, Sarvpreet Kaur, Aman Kumar Mahto, Rikeshwer Prasad Dewangan, J. Shankaraswamy, Sarika Saxena
Summary: This study provides the first evidence of human telomeric G4 destabilization upon peptide binding, which will open new research avenues for treating DNA-related diseases.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Di Bai, Song-Wang Shan, Xin Zhang, Yan Li, Jie Xie, Wen-Qiang Wu
Summary: In this study, the folding, dynamics induced by environment, and protein-catalyzed unfolding of plant telomeric G4s were comprehensively studied. It was found that various plant telomeric sequences can fold into G4 structures, and the stability of G4s in dilute solution is decreased by both 5' and 3' ssDNA. Molecular crowding promotes the formation of parallel structures for three-layer G4s and increases the stability of all selected G4s. AtRecQ2 helicase can resolve the stable parallel structure of typical plant telomeric G4 in crowded solution, while ssDNA binding protein AtRPA cannot. Furthermore, AtRecQ2 unwinds the structure more efficiently in the presence of AtRPA. These results expand our understanding of the structures and dynamics of plant telomeric G4s.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Luca Bertini, Valeria Libera, Francesca Ripanti, Francesca Natali, Marco Paolantoni, Andrea Orecchini, Alessandro Nucara, Caterina Petrillo, Lucia Comez, Alessandro Paciaroni
Summary: Telomeric G-quadruplexes (G4s) exhibit structural polymorphism and the dynamics of G4s are affected by conformation and complexation. In this study, the dynamics of Tel22 in different conformations and complexed with BRACO19 ligand were investigated. The results showed that hydration water played a role in mediating the effect of polymorphism and complexation on the fast dynamics of G4s.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Applied
Jielin Chen, Mingpan Cheng, Jiawei Wang, Dehui Qiu, David Monchaud, Jean-Louis Mergny, Huangxian Ju, Jun Zhou
Summary: The structural integrity of the 3'-end G-quartet is necessary for G4s to be catalytically competent, and G-vacancy-mediated catalytic activity losses can be remediated via the G-vacancy complementation strategy. Furthermore, the terminal G-quartet can act as a proximal coordinating group and cooperate with the flanking nucleotide to activate the hemin cofactor.
CHINESE JOURNAL OF CATALYSIS
(2021)
Article
Biochemistry & Molecular Biology
Tapas Paul, Andrew F. Voter, Rachel R. Cueny, Momcilo Gavrilov, Taekjip Ha, James L. Keck, Sua Myong
NUCLEIC ACIDS RESEARCH
(2020)
Editorial Material
Health Care Sciences & Services
Hossein Zare, Ge Bai, Corey Albrecht, Joshua L. Choe, Gerard F. Anderson
POPULATION HEALTH MANAGEMENT
(2021)
Article
Biophysics
Tapas Paul, Taekjip Ha, Sua Myong
Summary: This study presents strategies for regenerating PEG surfaces for multiple rounds of experiments, including washing out bound proteins, reannealing double-stranded DNA, and stripping off NeutrAvidin to regenerate the biotin-PEG layer. These methods enhance the efficiency of single-molecule experiments.
BIOPHYSICAL JOURNAL
(2021)
Editorial Material
Health Care Sciences & Services
Joshua L. Choe, Antonio J. Trujillo, Gerard F. Anderson
POPULATION HEALTH MANAGEMENT
(2021)
Article
Multidisciplinary Sciences
Tulin Dadali, Anne R. Diers, Shiva Kazerounian, Senthil K. Muthuswamy, Pallavi Awate, Ryan Ng, Saie Mogre, Carrie Spencer, Katerina Krumova, Hannah E. Rockwell, Justice McDaniel, Emily Y. Chen, Fei Gao, Karl T. Diedrich, Vijetha Vemulapalli, Leonardo O. Rodrigues, Viatcheslav R. Akmaev, Khampaseuth Thapa, Manuel Hidalgo, Arindam Bose, Vivek K. Vishnudas, A. James Moser, Elder Granger, Michael A. Kiebish, Stephane Gesta, Niven R. Narain, Rangaprasad Sarangarajan
Summary: Reactive oxygen species (ROS) play a role in triggering cell signaling events to promote and maintain tumorigenicity. Chemotherapy and radiation can induce ROS to elicit cell death, making it possible to target ROS pathways for effective anti-cancer therapeutics. Coenzyme Q(10) is shown to increase ROS generation when delivered to increase mitochondrial Q-pool, resulting in anti-cancer effects in a pancreatic cancer model.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Multidisciplinary
Honghe Liu, Yu-Ning Lu, Tapas Paul, Goran Periz, Michael T. Banco, Adrian R. Ferre-D'Amare, Jeffrey D. Rothstein, Lindsey R. Hayes, Sua Myong, Jiou Wang
Summary: DHX36 is a robust positive regulator of C9orf72 RAN translation, facilitating the process by resolving repeat RNA G-quadruplex structures. It may serve as a potential target for therapeutic intervention in ALS and FTD associated with C9orf72 expansions.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Genetics & Heredity
Samantha L. Sanford, Griffin A. Welfer, Bret D. Freudenthal, Patricia L. Opresko
Summary: Telomeres at the ends of linear chromosomes are essential for genome maintenance and cellular proliferation, but shorten with each cell division. Telomerase compensates for this by lengthening the telomeric 3' single strand overhang, and has the unique ability to synthesize multiple GGTTAG repeats in a process called repeat addition processivity. Understanding telomerase's unique properties and catalytic mechanism may help in selectively manipulating telomerase activity for therapeutic purposes, particularly in cancer treatment.
Article
Biochemistry & Molecular Biology
Hai Pan, Parminder Kaur, Ryan Barnes, Ariana C. Detwiler, Samantha Lynn Sanford, Ming Liu, Pengning Xu, Chelsea Mahn, Qingyu Tang, Pengyu Hao, Dhruv Bhattaram, Changjiang You, Xinyun Gu, Warren Lu, Jacob Piehler, Guozhou Xu, Keith Weninger, Robert Riehn, Patricia L. Opresko, Hong Wang
Summary: This study reveals that the interaction between TIN2 and TRF1 promotes DNA compaction and DNA-DNA bridging in a telomeric sequence- and length-dependent manner. Short telomeric DNA substrates exhibit transient TRF1-mediated telomeric DNA-DNA bridging events, while longer substrates show stable TRF1-mediated DNA-DNA bridging events. Tankyrase 1 and NAD+ can modulate TRF1-TIN2 mediated DNA-DNA bridging, while TPP1 inhibits TRF1-TIN2L-mediated DNA-DNA bridging. These findings suggest a molecular model where protein assemblies at telomeres are heterogeneous with distinct subcomplexes and play different roles in telomere protection and elongation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Tapas Paul, Wilson Liou, Xinyi Cai, Patricia L. Opresko, Sua Myong
Summary: Research has found that POT1 has an unexpected activity in imparting dynamic structure to the telomere overhang, especially when interacting with TRF2. TRF2 can recruit POT1-bound overhangs to the telomere ds/ss junction and induce stepwise movement along the axis of the telomere duplex, with the same steps observed regardless of overhang length, implying a tightly regulated conformational dynamic coordinated by TRF2 and POT1.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Chemistry, Physical
Tapas Paul, Priyabrat Mohapatra, Padmaja Prasad Mishra
Summary: The study systematically investigated the adsorption mechanism of oligonucleotides on GO and GO-AuNP hybrid surface, with higher efficiency and rate of adsorption found for the hybrid material. Results showed that ds-DNA adsorbs on the GO-AuNP hybrid material by completely unzipping the strands, while no clear evidence was observed for GO.
APPLIED SURFACE SCIENCE
(2022)
Article
Oncology
Jeffrey Patterson-Fortin, Arindam Bose, Wei-Chih Tsai, Carter Grochala, Huy Nguyen, Jia Zhou, Kalindi Parmar, Jean-Bernard Lazaro, Joyce Liu, Kelsey McQueen, Geoffrey I. Shapiro, David Kozono, Alan D. D'Andrea
Summary: Inhibitors of DNA repair pathways, such as peposertib, show promise as anticancer drugs. This study identified POLQ and genes in the MMEJ pathway as key predictors of sensitivity to DNA-PK inhibition. Combined treatment with peposertib and a POLO inhibitor resulted in synthetic lethality in TP53-deficient tumor cell lines, suggesting a potential treatment strategy for TP53-mutant solid tumors.
Article
Biochemical Research Methods
Tapas Paul, Sua Myong
Summary: This article presents an efficient and reliable protocol for generating and regenerating PEG surfaces for multiple rounds of experiments. The protocol is simple, rapid, and versatile, and it saves time and enhances the efficiency of the experiments.
Article
Health Care Sciences & Services
Jeromie Ballreich, Ijeamaka Ezebilo, Banda Abdallah Khatifa, Joshua Choe, Gerard Anderson
Summary: There is significant variation in coverage guidelines for the genetic therapies nusinersen and onasemnogene abeparvovec across fee-for-service state Medicaid programs. Differences exist in diagnostic requirements, SMN2 gene count, and ventilator status. States with more restrictive guidelines have lower utilization of nusinersen.
JOURNAL OF MANAGED CARE & SPECIALTY PHARMACY
(2022)