Article
Biochemistry & Molecular Biology
Corey R. Nelson, Tyler Mrozowich, Sean M. Park, Simmone D'souza, Amy Henrickson, Justin R. J. Vigar, Hans-Joachim Wieden, Raymond J. Owens, Borries Demeler, Trushar R. Patel
Summary: This study demonstrates that DDX17 can directly interact with and unwind RVFV non-coding RNA regions IGR and NCR, providing important insights into the mechanism by which DDX17 restricts RVFV replication.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Wei Yuan, Qais Al-Hadid, Zhihao Wang, Lei Shen, Hyejin Cho, Xiwei Wu, Yanzhong Yang
Summary: R-loops, composed of DNA/RNA hybrid and single-stranded DNA, are recognized as critical regulators in chromatin biology, particularly enriched at gene promoters for regulating gene expression. TDRD3 interacts with DHX9 to recruit it to gene promoters, resolving R-loops and facilitating gene expression. Additionally, TDRD3 stimulates the helicase activity of DHX9, working together with TOP3B to suppress promoter-associated R loops.
NUCLEIC ACIDS RESEARCH
(2021)
Correction
Cell Biology
Carmen Perez-Calero, Aleix Bayona-Feliu, Xiaoyu Xue, Sonia I. Barroso, Sergio Munoz, Victor M. Gonzalez-Basallote, Patrick Sung, Andres Aguilera
Summary: In the process of preparing Supplemental Figure S7D for the final version of the article, two of the DRIPc-seq profiles were unintentionally plotted with a different bin size. The amended version of the figure has been marked with RNH-sensitive regions and can be found in the Revised Supplemental Material online. The revised plots correspond to the original data and do not change the conclusions of the paper.
GENES & DEVELOPMENT
(2021)
Article
Biochemistry & Molecular Biology
Corey Nelson, Tyler Mrozowich, Darren L. Gemmill, Sean M. Park, Trushar R. Patel
Summary: The study demonstrates that DEAD-box helicase DDX3X can directly interact with and unwind flaviviral TRs in vitro. Therefore, DDX3X may be further explored as a therapeutic target to inhibit Flaviviral replication.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Lidia Chellini, Marco Pieraccioli, Claudio Sette, Maria Paola Paronetto
Summary: DHX9 plays an important role in the development of prostate cancer, with up-regulation of DHX9 correlating with advanced stage and poor prognosis. The limited treatment options for patients in the castration-resistant stage make DHX9 a potential new druggable target.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Genetics & Heredity
Xiaoxiao Wang, Sufang Zhang, Zhongtao Zhang, Nayef A. Mazloum, Ernest Y. C. Lee, Marietta Y. W. Lee
Summary: The study aimed to test the hypotheses that D-loop extension in homology directed repair (HDR) is facilitated by DHX9 and that its recruitment is mediated by protein-protein interactions between DHX9 and Pol delta 4 and/or PCNA. The results showed that DHX9 strongly stimulated Pol delta 4 mediated D-loop extension and direct interactions between DHX9 and PCNA as well as Pol delta 4 subunits were observed. These findings suggest that DHX9 is recruited by Pol delta 4/PCNA to facilitate D-loop synthesis in HDR and plays a role in cellular HDR.
Article
Chemistry, Multidisciplinary
Feng Tang, Yinan Wang, Zi Gao, Shiyuan Guo, Yinsheng Wang
Summary: This study reveals the interaction between DNA polymerase eta and DHX9 and demonstrates that this interaction promotes the replicative bypass of G4 structures in chromatin.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Multidisciplinary Sciences
Nanfang Huang, Yang Song, Wenhui Shi, Juan Guo, Lingyun Wu, Zheng Zhang, Qi He, Xiao Li, Feng Xu
Summary: DHX9 overexpression in myelodysplastic syndromes (MDS) is associated with poor prognosis and high risk of acute myeloid leukemia (AML) transformation. DHX9 is essential for malignant proliferation of leukemia cells. Suppression of DHX9 increases cell apoptosis and sensitizes cells to chemotherapy. Additionally, DHX9 knockdown inactivates PI3K-AKT and ATR-Chk1 signaling, promotes R-loop accumulation, and leads to R-loop-mediated DNA damage.
Article
Biochemistry & Molecular Biology
Mei-Yin Liu, Keng-Ru Lin, Yuh-Ling Chien, Bing-Ze Yang, Li-Yu Tsui, Hsueh-Ping Catherine Chu, Ching-Shyi Peter Wu
Summary: In this study, we uncover a new mechanism by which ATR directly regulates DHX9 through phosphorylation to eliminate stress-induced R-loops. Phosphorylation of DHX9 at S321 promotes its interaction with gamma H2AX, BRCA1 and RPA, and is required for its association with R-loops under genotoxic stress. Cells expressing the non-phosphorylatable DHX9S321A variant exhibit hypersensitivity to genotoxic stress, while those expressing the phosphomimetic DHX9S321D variant prevent R-loop accumulation and display resistance to DNA damage agents.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Xu-hui Zhu, Bao-fei Sun, Mei Luo, Jia Yu, Yun-dong Zhang, Hou-qiang Xu, Heng Luo
Summary: The G-quadruplex DNA structure in cancer cells requires the involvement of DNA helicase for unwinding, and the helicase can bind to and unwind G4DNA. The binding and unwinding of G4DNA by helicase is influenced by the single-stranded DNA terminals in G4DNA.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Cell Biology
Kejia Wu, Yiqi Zhang, Yuxin Liu, Qingxiu Li, Yong Chen, Juan Chen, Changzhu Duan
Summary: In this study, elevated levels of UHRF2 protein were observed in HBV-associated HCC cells and tissues. UHRF2 overexpression promoted the viability, proliferation, migration, and invasiveness of HBV-positive HCC cells, and enhanced HBV DNA replication. Phosphorylation of UHRF2 by HBx at S643 acted as a switch in HBV-associated HCC oncogenesis, activating the positive feedback between phosphorylated UHRF2 and HBV, indicating that UHRF2 could serve as a potential prognostic indicator for HBV-associated HCC.
CELL DEATH DISCOVERY
(2023)
Article
Cell Biology
Huangfu Ning, Hongchuang Ma, Mengyun Tian, Jie Zhang, Yong Wang, Zhenwei Li, Xiaomin Chen, Hanbin Cui
Summary: This study found that DHX9 expression is significantly increased in macrophages and PBMCs from patients with AS, and its interaction with p65 enhances the transcriptional activity of inflammatory factors. Knockdown of DHX9 alleviates AS progression in a mouse model. The results suggest DHX9 as a potential target for developing therapeutic strategies for AS.
Article
Multidisciplinary Sciences
Xingxing Ren, Decai Wang, Guorong Zhang, Tingyue Zhou, Zheng Wei, Yi Yang, Yunjiang Zheng, Xuqiu Lei, Wanyin Tao, Anmin Wang, Mingsong Li, Richard A. Flavell, Shu Zhu
Summary: RNA helicase DHX9 is a transcriptional regulator and recognizes RNA viruses in the cytoplasm. Knockout mice studies show that DHX9 is crucial for host resistance to RNA virus infections. Mechanistically, DHX9 directly binds to STAT1 and recruits Pol II to participate in the transcription of interferon-stimulated genes (ISGs).
Article
Genetics & Heredity
Daniel G. Calame, Tianyu Guo, Chen Wang, Lillian Garrett, Angad Jolly, Moez Dawood, Alina Kurolap, Noa Zunz Henig, Jawid M. Fatih, Isabella Herman, Haowei Du, Tadahiro Mitani, Lore Becker, Birgit Rathkolb, Raffaele Gerlini, Claudia Seisenberger, Susan Marschall, Jill Hunter, Amanda Gerard, Alexis Heidlebaugh, Thomas Challman, Rebecca C. Spillmann, Shalini N. Jhangiani, Zeynep Coban-Akdemir, Seema Lalani, Lingxiao Liu, Anya Revah-Politi, Alejandro Iglesias, Edwin Guzman, Evan Baugh, Nathalie Boddaert, Sophie Rondeau, Clothide Ormieres, Giulia Barcia, Queenie K. G. Tan, Sophie Isabelle Thiffault, Tomi Pastinen, Kazim Sheikh, Suur Biliciler, Davide Mei, Federico Melani, Vandana Shashi, Yuval Yaron, Mary Steele, Emma Wakeling, Elsebet Ostergaard, Francisca Undiagnosed Dis Network, Francisca Millan, Teresa Santiago-Sim, Julien Thevenon, Ange-Line Bruel, Christel Thauvin-Robinet, Denny Popp, Konrad Platzer, Pawel Gawlinski, Wojciech Wiszniewski, Dana Marafi, Davut Pehlivan, Jennifer E. Posey, Richard A. Gibbs, Valerie Gailus-Durner, Renzo Guerrini, Helmut Fuchs, Martin Hrabe de Angelis, Sabine M. Hoelter, Hoi-Hung Cheung, Shen Gu, James R. Lupski
Summary: DExD/H-box RNA helicases (DDX/DHX) are part of a large gene family that encodes enzymes and variations in these genes can lead to neurodevelopmental disorders and cancer. By analyzing genetic data, researchers found rare variants in the DHX9 gene in individuals with different disorders ranging from neurodevelopmental disorders to a specific type of polyneuropathy. Further experiments confirmed that DHX9 is important for neurodevelopment and neuronal homeostasis.
AMERICAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Multidisciplinary Sciences
Prasun Chakraborty, Kevin Hiom
Summary: DHX9 is a critical player in the repair of DNA damage by homologous recombination, promoting the recruitment of BRCA1 during transcription and facilitating end-resection of DSB.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Uttam Sharma, Tushar Singh Barwal, Akanksha Khandelwal, Akshay Malhotra, Manjit Kaur Rana, Amrit Pal Singh Rana, Evgeny N. Imyanitov, Karen M. Vasquez, Aklank Jain
Summary: The expression of ZFAS1 is significantly downregulated in TNBC patients, promoting cell proliferation and colonization by affecting cell cycle-dependent kinase inhibitors and epithelial/mesenchymal markers. ZFAS1 may function as a tumor-suppressor lncRNA and provide a new therapeutic target for TNBC patients.
Review
Biochemistry & Molecular Biology
Chris A. Brosey, Jerry H. Houl, Panagiotis Katsonis, Lakshitha P. F. Balapiti-Modarage, Shobanbabu Bommagani, Andy Arvai, Davide Moiani, Albino Bacolla, Todd Link, Leslie S. Warden, Olivier Lichtarge, Darin E. Jones, Zamal Ahmed, John A. Tainer
Summary: The study investigated the structure of CoV-2 Mac1 and its relationship with the human DNA-damage signaling factor PARG, leading to the discovery of two novel compounds, PARG-345 and PARG-329, which crystallize within the Mac1 active site, providing critical structure-activity data.
PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Hridayesh Prakash, Dilip Upadhyay, Obul Reddy Bandapalli, Aklank Jain, Burkhard Kleuser
Summary: Sphingolipids, including S1P and Ceramide, play a crucial role in respiratory bacterial infections, and potential control of SARSCoV-2 infection may involve targeting S1P signaling and utilizing other sphingolipid derivatives such as Ceramide-1 Phosphate.
PROSTAGLANDINS & OTHER LIPID MEDIATORS
(2021)
Review
Biochemistry & Molecular Biology
Tushar Singh Barwal, Uttam Sharma, Sonali Bazala, Ipsa Singh, Manju Jain, Hridayesh Prakash, Shashank Shekhar, Elise N. Sandberg, Anupam Bishayee, Aklank Jain
Summary: The article discusses the use of aromatase inhibitors in breast and ovarian cancers, as well as the potential role of noncoding RNAs (including miRNAs and lncRNAs) in modulating cancer hallmarks and overcoming drug resistance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Immunology
Roshan Kumar Roy, Rakhi Yadav, Aklank Jain, Vishwas Tripathi, Manju Jain, Sandhya Singh, Hridayesh Prakash
Summary: Immunological memory is essential for prolonged immunity, with central memory maintaining immunity for specific infections and effector memory controlling local infections. The generation of long-lived plasma cells is crucial for producing neutralizing antibodies to enhance immune recall.
INTERNATIONAL REVIEWS OF IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Shahid Banday, Raj K. Pandita, Arjamand Mushtaq, Albino Bacolla, Ulfat Syed Mir, Dharmendra Kumar Singh, Sadaf Jan, Krishna P. Bhat, Clayton R. Hunt, Ganesh Rao, Vijay K. Charaka, John A. Tainer, Tej K. Pandita, Mohammad Altaf
Summary: Vigilin plays a crucial role in DNA damage repair in cells, with its depletion leading to increased sensitivity to cisplatin or ionizing radiation-induced cell death and genomic instability. This depletion also affects the repair process of DNA breaks and the recruitment of DDR proteins RAD51 and BRCA1 to DNA damage sites.
MOLECULAR AND CELLULAR BIOLOGY
(2021)
Article
Oncology
Apoorva Bangroo, Akshay Malhotra, Uttam Sharma, Aklank Jain, Anupreet Kaur
Summary: Zinc oxide nanomaterials, synthesized biologically, demonstrate potential as effective and environmentally friendly anticancer agents, showing a reduction in viable breast cancer cells in vitro. This study marks a significant step in utilizing molar concentrations of synthesized zinc oxide nanomaterials for potential clinical use in breast cancer treatment.
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL
(2022)
Article
Multidisciplinary Sciences
Zu Ye, Shengfeng Xu, Yin Shi, Albino Bacolla, Aleem Syed, Davide Moiani, Chi-Lin Tsai, Qiang Shen, Guang Peng, Paul G. Leonard, Darin E. Jones, Bin Wang, John A. Tainer, Zamal Ahmed
Summary: In this study, GRB2 was found to play a crucial role in DNA double-strand break repair by forming a complex with MRE11 to promote efficient homology-directed repair initiation and releasing MRE11 through ubiquitination. Depletion of RBBP6 leads to prolonged HDR defects, highlighting GRB2's importance in the repair process.
Article
Genetics & Heredity
Mengling Qi, Peter D. Stenson, Edward Ball, John A. Tainer, Albino Bacolla, Hildegard Kehrer-Sawatzki, David N. Cooper, Huiying Zhao
Summary: Microdeletions and gross deletions are important causes of human inherited disease, and their genomic locations are influenced by the DNA sequence environment. This study analyzed the DNA sequences near breakpoint junctions and found correlations between the frequencies of non-B DNA-forming repeats, GC-content, specific sequence motifs, and deletion length. The study also proposed using a deletion length cut-off of 25-30 bp to functionally distinguish microdeletions from gross deletions.
Article
Biochemistry & Molecular Biology
Ning Tsao, Joshua R. Brickner, Rebecca Rodell, Adit Ganguly, Matthew Wood, Clement Oyeniran, Tanveer Ahmad, Hua Sun, Albino Bacolla, Lisheng Zhang, Valentina Lukinovic, Jennifer M. Soll, Brittany A. Townley, Alexandre G. Casanova, John A. Tainer, Chuan He, Alessandro Vindigni, Nicolas Reynoird, Nima Mosammaparast
Summary: The study found that RNA alkylation serves as the initiating signal for the ASCC-ALKBH3 repair pathway, crucial for recruiting ASCC. It was demonstrated that alkylated RNA can activate RNF113A E3 ligase, suppressing transcription and R-loop formation. This research reveals the significant role of RNA damage in eliciting a specific response to genotoxins.
Article
Multidisciplinary Sciences
Shyam Twayana, Albino Bacolla, Angelica Barreto-Galvez, Ruth B. De-Paula, William C. Drosopoulos, Settapong T. Kosiyatrakul, Eric E. Bouhassira, John A. Tainer, Advaitha Madireddy, Carl L. Schildkraut
Summary: The study reveals the crucial role of Pol eta in the replication of common fragile sites (CFSs), highlighting how its deficiency can lead to replication pausing and genetic variations. Presence of non-B DNA structures may increase replication hindrance. Activity of Pol eta in replicating through CFSs may result in genetic variations found in the human population at these sites.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Genetics & Heredity
Cong Fan, Ken Chen, Yukai Wang, Edward Ball, Peter D. Stenson, Matthew Mort, Albino Bacolla, Hildegard Kehrer-Sawatzki, John A. Tainer, David N. Cooper, Huiying Zhao
Summary: This study systematically analyzed key topological features at the DNA, RNA, and protein levels in order to construct a tool for distinguishing pathogenic repeat expansions. Pathogenic repeat expansions were found to exhibit specific features at the DNA, RNA, and protein levels and exert a synergistic influence on the gene expression pathway.
Article
Biochemistry & Molecular Biology
Aleem Syed, Frantisek Filandr, Jeffrey Patterson-Fortin, Albino Bacolla, Ramya Ravindranathan, Jia Zhou, Drew T. Mcdonald, Mohammed E. Albuhluli, Amy Verway-Cohen, Joseph A. Newman, Miaw-Sheue Tsai, Darin E. Jones, David C. Schriemer, Alan D. D'Andrea, John A. Tainer
Summary: Polymerase theta (Pol θ) is involved in DNA replication and repair, and its inhibition is deadly for BRCA1 and BRCA2-deficient tumor cells. Novobiocin (NVB), an ATPase inhibitor of Pol θ, is being tested as an anti-cancer drug in clinical trials. This study reveals the molecular mechanism of NVB-mediated Pol θ inhibition, showing that NVB blocks DNA binding by binding to an allosteric site.
NUCLEIC ACIDS RESEARCH
(2023)
Correction
Biochemistry & Molecular Biology
A. Bacolla
NUCLEIC ACIDS RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Atanu Mondal, Apoorva Bhattacharya, Vipin Singh, Shruti Pandita, Albino Bacolla, Raj K. Pandita, John A. Tainer, Kenneth S. Ramos, Tej K. Pandita, Chandrima Das
Summary: From initiation to progression, cancer cells experience a variety of internal and external stresses, leading to changes in their epigenome and transcriptome. Understanding the stress response pathways of cancer cells is crucial for developing novel anticancer therapies.
MOLECULAR AND CELLULAR BIOLOGY
(2022)