Article
Biochemistry & Molecular Biology
Juliette A. Kamp, Bennie B. L. G. Lemmens, Ron J. Romeijn, Roman Gonzalez-Prieto, Jesper Olsen, Alfred C. O. Vertegaal, Robin van Schendel, Marcel Tijsterman
Summary: This study uncovers the crosstalk between RNA surveillance and DNA repair in living animals, revealing the role of SMG-1 in this process through genetic screens and genome-wide analyses. The findings shed light on how defects in RNA processing can affect DNA repair, and highlight the importance of SMG-1 in regulating this interaction.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Aruna S. Jaiswal, Arijit Dutta, Gayathri Srinivasan, Yaxia Yuan, Daohong Zhou, Montaser Shaheen, Doraid T. Sadideen, Austin Kirby, Elizabeth A. Williamson, Yogesh K. Gupta, Shaun K. Olsen, Mingjiang Xu, Eva Loranc, Pramiti Mukhopadhyay, Alexander Pertsemlidis, Alexander J. R. Bishop, Patrick Sung, Jac A. Nickoloff, Robert Hromas
Summary: BRCA1-deficient cells show increased IRE1 RNase activity and degradation of microRNAs, leading to cellular dysfunction. miR-4638-5p represses TATDN2 expression, resulting in synthetic lethality in BRCA1-deficient cancer cells. TATDN2 has the ability to resolve R-loops and is essential for the survival of BRCA1-deficient cancer cells.
NUCLEIC ACIDS RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Joshua R. Brickner, Jada L. Garzon, Karlene A. Cimprich
Summary: R-loops, non-B DNA structures formed during transcription, can cause genomic instability but also have regulatory roles in maintaining genome integrity. They contribute to genomic instability during DNA replication and double-strand break repair, but also participate as intermediates in repair and influence pathway choice. Additionally, R-loops may be linked to disease.
Editorial Material
Cell Biology
Jenna M. Frame, Trista E. North
Summary: This study uncovers that loss of DEAD-box helicase Ddx41 triggers an inflammatory cascade mediated by R-loop during embryonic development, promoting HSPC production. Human studies suggest conservation of this inflammatory mechanism in DDX41-associated hematologic diseases, providing a potential avenue for future therapeutic interventions.
DEVELOPMENTAL CELL
(2021)
Article
Biochemistry & Molecular Biology
Natalie Laspata, Parminder Kaur, Sofiane Yacine Mersaoui, Daniela Muoio, Zhiyan Silvia Liu, Maxwell Henry Bannister, Hai Dang Nguyen, Caroline Curry, John M. Pascal, Guy G. Poirier, Hong Wang, Jean-Yves Masson, Elise Fouquerel
Summary: PARP1 is a DNA-dependent ADP-Ribose transferase that is involved in resolving DNA breaks and non-B DNA structures. It has been identified as a component of the R-loop-associated protein-protein interaction network, suggesting its potential role in resolving R-loop structures. R-loops are three-stranded nucleic acid structures that can cause genome instability if persistently unresolved.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Cell Biology
Joshua T. Weinreb, Noura Ghazale, Kith Pradhan, Varun Gupta, Kathryn S. Potts, Brad Tricomi, Noah J. Daniels, Richard A. Padgett, Sofia De Oliveira, Amit Verma, Teresa Bowman
Summary: Hematopoietic stem and progenitor cells are crucial for blood and immune system maintenance throughout life. The DEAD-box helicase 41 (Ddx41) plays a key role in regulating HSPC production by suppressing the accumulation of R-loops, thus preventing inflammatory signaling pathways and maintaining cellular fitness. This study suggests a possible conservation of mechanism in human cells with decreased DDX41.
DEVELOPMENTAL CELL
(2021)
Article
Chemistry, Multidisciplinary
Xiaomei He, Jun Yuan, Zi Gao, Yinsheng Wang
Summary: R-loops and DNA G4 structures are enriched in gene promoter regions, and U2AF1 can bind directly to these structures. Binding with R-loops stimulates U2AF1's phase separation and modulates cotranscriptional pre-mRNA splicing.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Tiziana Bruno, Giacomo Corleone, Valeria Catena, Clelia Cortile, Francesca De Nicola, Francesca Fabretti, Svitlana Gumenyuk, Francesco Pisani, Andrea Mengarelli, Claudio Passananti, Maurizio Fanciulli
Summary: This study reveals that the RNA-binding protein Che-1 interacts with paraspeckles through NEAT1 and localizes on R-loops in Multiple Myeloma. Depletion of Che-1 leads to the accumulation of RNA:DNA hybrids and activation of a systemic inflammatory response, with poor prognosis. The study suggests that Che-1/NEAT1 cooperation is crucial for preventing excessive inflammatory signaling and maintaining genome stability.
Article
Biochemistry & Molecular Biology
Jonathan Heuze, Samira Kemiha, Antoine Barthe, Alba Toran Vilarrubias, Elyes Aouadi, Umberto Aiello, Domenico Libri, Yea-Lih Lin, Armelle Lengronne, Jerome Poli, Philippe Pasero
Summary: R-loops, RNA:DNA hybrids, act as barriers to replication forks and interfere with postreplicative fork repair mechanisms if not promptly degraded by RNase H. Cells lacking RNase H exhibit impaired replication under challenging conditions, and triptolide, an inhibitor of transcription, restores fork resection.
Article
Multidisciplinary Sciences
Greg H. P. Ngo, Julia W. Grimstead, Duncan M. Baird
Summary: DNA-RNA hybrid structures have been found near DNA double-strand breaks within transcriptional active regions of the genome, affecting the repair of these breaks. R loops, containing DNA-RNA hybrids and displaced ssDNA, can form at sub-telomeric DSBs independently of DNA resection and are induced alongside two-stranded DNA-RNA hybrids that form on ssDNA generated by DNA resection. UPF1, an RNA/DNA helicase, is identified as a crucial factor driving the formation of R loops and DNA-RNA hybrids to stimulate DNA repair processes.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Despoina Sakellariou, Sara Thornby Bak, Esin Isik, Sonia Barroso, Antonio Porro, Andres Aguilera, Jiri Bartek, Pavel Janscak, Javier Pena-Diaz
Summary: The study reveals that the mismatch repair protein MutS beta is enriched at telomeres in ALT cancer cells, preventing the accumulation of G-quadruplex (G4) structures and R-loops, thus maintaining telomere integrity during alternative lengthening of telomeres.
Article
Thermodynamics
Wei Zhou, Jin Chen
Summary: This study analyzes the overall performance of China's listed Energy Technology and Engineering (ETE) enterprises, proposing a double hierarchy network model to integrate operation management and stock performance. It is found that enterprises with positive endogenous R&D elasticity are more likely to seize opportunities and survive in the face of external uncertainties, while also showing stable performance in the recent 5 years. Further strategies are provided for ETE managers and investors interested in this industry, considering specific external factors that could impact the ETE industry.
Article
Multidisciplinary Sciences
Yang Liu, Lu Wang, Xin Xu, Yue Yuan, Bo Zhang, Zeyang Li, Yuchen Xie, Rui Yan, Zeqi Zheng, Jianguo Ji, Johanne M. Murray, Antony M. Carr, Daochun Kong
Summary: This study reveals the mechanism by which the checkpoint kinases Rad3ATR and Cds1Chk2 directly regulate the replicative helicase under replication stress. When replication forks stall, Cds1Chk2 phosphorylates Cdc45, reducing CMG helicase activity and preserving the integrity of stalled replisomes and replication forks.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Laura C. Funk, Jun Wan, Sean D. Ryan, Charanjeet Kaur, Ruth Sullivan, Avtar Roopra, Beth A. Weaver
Summary: Chromosomal instability is a hallmark of cancer, with high levels of CIN causing cell death and tumor suppression. The tumor suppressor p53 is not required for high CIN-induced tumor suppression, as demonstrated by pharmacological induction of high CIN resulting in cell death independently of p53 function.
MOLECULAR CANCER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Ru-Xuan Tsai, Kuo-Chen Fang, Po-Cheng Yang, Yu-Hung Hsieh, I-Tien Chiang, Yunfei Chen, Hun-Goo Lee, Jeannie T. Lee, Hsueh-Ping Catherine Chu
Summary: TERRA is an RNA molecule that interacts with the chromatin remodeler ATRX and plays a role in regulating genome stability and transcription. It maintains the stability of DNA G-quadruplex structures and prevents ATRX from binding to subtelomeric regions, thereby repressing H3K9me3 formation. Depletion of TERRA leads to a decrease in G-quadruplex abundance at transcription start sites (TSS), which is associated with increased ATRX occupancy and differential gene expression. Loss of ATRX alleviates the gene repression caused by TERRA depletion, while knockdown of TERRA diminishes DNA G-quadruplex signals and silencing of ATRX increases G-quadruplex formation.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Erika Chacin, Priyanka Bansal, Karl-Uwe Reusswig, Luis M. Diaz-Santin, Pedro Ortega, Petra Vizjak, Belen Gomez-Gonzalez, Felix Mueller-Planitz, Andres Aguilera, Boris Pfander, Alan C. M. Cheung, Christoph F. Kurat
Summary: Yta7 is a chromatin remodeling enzyme that promotes chromosome replication during S phase, forming hexameric complexes capable of segregating histones from DNA. Its enzymatic activity is regulated by S phase-forms of Cyclin-Dependent Kinase (S-CDK), which stimulates ATP hydrolysis by Yta7 to promote nucleosome disassembly and chromatin replication. These findings present a mechanism for how cells coordinate chromatin dynamics with the cell cycle machinery to ensure genome duplication during S phase.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Marta San Martin-Alonso, Maria E. Soler-Oliva, Maria Garcia-Rubio, Tatiana Garcia-Muse, Andres Aguilera
Summary: The authors have identified that R-loops are formed during transcription in different ways and cells have specialized mechanisms to prevent their formation, with one major mechanism being independent of DNA replication and another one being linked to DNA replication.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Sonia Jimeno, Rosario Prados-Carvajal, Maria Jesus Fernandez-Avila, Sonia Silva, Domenico Alessandro Silvestris, Martin Endara-Coll, Judit Domingo-Prim, Fernando Mejias-Navarro, Guillermo Rodriguez-Real, Amador Romero-Franco, Silvia Jimeno-Gonzalez, Sonia Barroso, Valeriana Cesarini, Andres Aguilera, Angela Gallo, Neus Visa, Pablo Huertas
Summary: Specific RNA-related factors, including the RNA-editing enzyme ADAR2, play important roles in DNA repair. The researchers found that RNA editing is involved in the response to DNA damage, with a phenomenon called the RNA Editing DAmage Response (REDAR) being observed. REDAR relies on the checkpoint kinase ATR and the recombination factor CtIP, and depletion of ADAR2 leads to increased cellular sensitivity to genotoxic agents and impaired homologous recombination.
NATURE COMMUNICATIONS
(2021)
Article
Genetics & Heredity
Pedro Ortega, Belen Gomez-Gonzalez, Andres Aguilera
Summary: Recent studies have shown the critical role of chromatin in both the occurrence and repair of DNA damage, particularly double-strand breaks. It is considered as a guardian of genome stability, which is altered in cancer cells.
Article
Biochemistry & Molecular Biology
Elena Galati, Maria C. Bosio, Daniele Novarina, Matteo Chiara, Giulia M. Bernini, Alessandro M. Mozzarelli, Maria L. Garcia-Rubio, Belen Gomez-Gonzalez, Andres Aguilera, Thomas Carzaniga, Marco Todisco, Tommaso Bellini, Giulia M. Nava, Gianmaria Frige, Sarah Sertic, David S. Horner, Anastasia Baryshnikova, Caterina Manzari, Anna M. D'Erchia, Graziano Pesole, Grant W. Brown, Marco Muzi-Falconi, Federico Lazzaro
Summary: This study identifies VID22 as a novel regulator of genome integrity in yeast cells, involved in DNA double-strand break repair and protection of G4-DNA structures. Loss of VID22 leads to increased levels of endogenous DNA damage and hypersensitivity to G4-stabilizing ligands.
NUCLEIC ACIDS RESEARCH
(2021)
Editorial Material
Biochemistry & Molecular Biology
Belen Gomez-Gonzalez, Arijit Dutta, Wenyi Feng
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Cell Biology
Despoina Sakellariou, Sara Thornby Bak, Esin Isik, Sonia Barroso, Antonio Porro, Andres Aguilera, Jiri Bartek, Pavel Janscak, Javier Pena-Diaz
Summary: The study reveals that the mismatch repair protein MutS beta is enriched at telomeres in ALT cancer cells, preventing the accumulation of G-quadruplex (G4) structures and R-loops, thus maintaining telomere integrity during alternative lengthening of telomeres.
Article
Multidisciplinary Sciences
Seong-Su Han, Kuo-Kuang Wen, Maria L. Garcia-Rubio, Marc S. Wold, Andres Aguilera, Wojciech Niedzwiedz, Yatin M. Vyas
Summary: This study identifies a crucial role for WASp in the DNA stress-resolution pathway, specifically in promoting the function of Replication Protein A at replication forks after DNA damage. Deficiency of WASp leads to RPA dysfunction, resulting in genomic instability.
NATURE COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Juan Carlos Canas, Maria Luisa Garcia-Rubio, Alicia Garcia, Francisco Antequera, Belen Gomez-Gonzalez, Andres Aguilera
Summary: The chromatin modifier Rtt109 plays a crucial role in the metabolism and repair of DNA-RNA hybrids and R-loops, with histone acetylation helping to prevent DNA damage and promote repair.
Article
Gastroenterology & Hepatology
Monica P. de Andres, Richard J. Jackson, Irene Felipe, Sladjana Zagorac, Christian Pilarsky, Anna Melissa Schlitter, Jaime Martinez de Villareal, Gun Ho Jang, Eithne Costello, Steve Gallinger, Paula Ghaneh, William Greenhalf, Thomas Knoesel, Daniel H. Palmer, Petra Ruemmele, Wilko Weichert, Markus Buechler, Thilo Hackert, John P. Neoptolemos, Faiyaz Notta, Nuria Malats, Paola Martinelli, Francisco X. Real
Summary: GATA4 and GATA6 cooperate to maintain the classical phenotype in pancreatic ductal adenocarcinoma (PDAC), and their expression is associated with patient prognosis and therapeutic response, providing a theoretical basis for using them as biomarkers of prognosis and therapeutic response.
Article
Multidisciplinary Sciences
Isidoro Cobo, Sumit Paliwal, Cristina Bodas, Irene Felipe, Julia Melia-Aloma, Ariadna Torres, Jaime Martinez-Villarreal, Marina Malumbres, Fernando Garcia, Irene Millan, Natalia del Pozo, Joo-Cheol Park, Ray J. MacDonald, Javier Munoz, Raul Mendez, Francisco X. Real
Summary: NFIC is a transcription factor that regulates the function of pancreatic acinar cells and suppresses the development of pancreatic ductal adenocarcinoma. It controls the differentiation and physiological functions of pancreatic acinar cells by regulating the expression of acinar genes, including those involved in RNA and protein metabolism, as well as the genes involved in resolving endoplasmic reticulum stress. In pancreatic cancer, NFIC expression is down-regulated, leading to the formation of pre-neoplastic lesions driven by mutant KRAS.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Belen Gomez-Gonzalez, Andres Aguilera
Summary: Double-strand breaks (DSBs) are highly harmful DNA damages that have significant effects on cell proliferation and genome integrity. Recent studies have shown that DSBs can enhance the formation of DNA-RNA hybrids, called break-induced RNA-DNA hybrids (BIRDHs). The source and impact of BIRDHs are still unresolved questions.
Article
Multidisciplinary Sciences
Aleix Bayona-Feliu, Emilia Herrera-Moyano, Nibal Badra-Fajardo, Ivan Galvan-Femenia, Maria Eugenia Soler-Oliva, Andres Aguilera
Summary: The chromatin network prevents genomic instability and mutagenic signatures associated with cancer by inhibiting R-loops and transcription-replication conflicts.
NATURE COMMUNICATIONS
(2023)
Meeting Abstract
Environmental Sciences
Sergio Munoz, Sonia Barroso, Javier Marqueta-Gracia, Maria Eugenia Soler, Andres Aguilera
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
(2022)
Meeting Abstract
Environmental Sciences
Andres Aguilera, Yesenia Rodriguez, Philip Hanawalt, Karlene A. Cimprich
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
(2022)