Article
Biochemistry & Molecular Biology
Tiffany S. Ma, Katja R. Worth, Conor Maher, Natalie Ng, Chiara Beghe, Natalia Gromak, Anna M. Rose, Ester M. Hammond
Summary: Hypoxia, a common feature of solid tumors, can lead to the accumulation of R-loops, which affects gene transcription and ribosomal RNA synthesis, playing a critical role in tumorigenesis.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Hong Zhou, Yapei Wang, Qing Wang, Le Li, Yan Hu, Yequn Wu, Mayank Gautam, Lijia Li
Summary: The study found that the occurrence of rDNA constriction was increased in human cancer cell lines compared to normal cells; decondensed rDNA was significantly enhanced after partial inhibition of rDNA transcription; transcription stress causes the accumulation of stable R-loops and subsequent constriction formation in the chromosomes.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Hongsha Guo, Gabriel Golczer, Ben S. Wittner, Adam Langenbucher, Marcus Zachariah, Taronish D. Dubash, Xin Hong, Valentine Comaills, Risa Burr, Richard Y. Ebright, Elad Horwitz, Joanna A. Vuille, Soroush Hajizadeh, Devon F. Wiley, Brittany A. Reeves, Jia-min Zhang, Kira L. Niederhoffer, Chenyue Lu, Benjamin Wesley, Uyen Ho, Linda T. Nieman, Mehmet Toner, Shobha Vasudevan, Lee Zou, Raul Mostoslavsky, Shyamala Maheswaran, Michael S. Lawrence, Daniel A. Harber
Summary: The deregulation of oncogenic signals in cancer triggers replication stress, which leads to the inhibition of IEG gene transcription by NR4A1. This results in proliferative failure and chromosomal instability, highlighting the potential role of NR4A1 in cancer progression.
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
Cell Biology
Mridul Budakoti, Abhay Shikhar Panwar, Diksha Molpa, Rahul Kunwar Singh, Dietrich Busselberg, Abhay Prakash Mishra, Henrique Douglas Melo Coutinho, Manisha Nigam
Summary: The discovery of micro RNAs in cancer has provided new insights for researchers in understanding their role as master regulators in controlling gene expression during various cellular processes, making them potential targets for cancer therapeutics.
CELLULAR SIGNALLING
(2021)
Article
Biochemistry & Molecular Biology
Marta San Martin Alonso, Sylvie M. Noordermeer
Summary: R-loops, RNA:DNA hybrids, play crucial roles in DNA repair processes, but excessive R-loop formation is linked to genetic instability. The multifaceted BRCA1 protein is recruited at DNA double-strand breaks to regulate R-loop removal, ensuring faithful repair processes.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Oncology
Fang Li, Alyan Zafar, Liang Luo, Ariana Maria Denning, Jun Gu, Ansley Bennett, Fenghua Yuan, Yanbin Zhang
Summary: R-loops are three-stranded structures consisting of an RNA-DNA hybrid and an unpaired single-stranded DNA, with biological implications in cellular physiology and pathological conditions. The accumulation of R-loops is associated with the development of various types of cancer, and studying their roles in cancer development is of great significance for innovative diagnostic and treatment approaches for cancer.
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
Biochemistry & Molecular Biology
Yang Liu, Qian Liu, Handong Su, Kunpeng Liu, Xue Xiao, Wei Li, Qianwen Sun, James A. Birchler, Fangpu Han
Summary: The study identified over 700,000 R-loop peaks in the maize genome, with sense R-loops mainly enriched in promoters and transcription termination sites. At the chromosome scale, maize R-loops were enriched in pericentromeric heterochromatin regions.
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
Cell Biology
Maria Moreno-del Alamo, Begona Carrasco, Ruben Torres, Juan Carlos Alonso
Summary: The study reveals that Bacillus subtilis PcrA interacts with RNA polymerase to mitigate replication-transcription conflicts. Depletion of PcrA can be partially suppressed by rnhB inactivation, but significantly reduces cell viability when rnhC or dinG are inactivated. PcrA, in collaboration with RnhC or DinG, plays a role in removing R-loops to preserve genomic integrity.
Article
Cell Biology
Takaaki Yasuhara, Reona Kato, Motohiro Yamauchi, Yuki Uchihara, Lee Zou, Kiyoshi Miyagawa, Atsushi Shibata
Summary: RAP80 is identified as a factor that suppresses the vulnerability of single-stranded DNA (ssDNA) in R-loops during DNA double-strand break (DSB) repair, preventing genomic abnormalities caused by harmful R-loop processing.
Article
Multidisciplinary Sciences
Ourania Chatzidoukaki, Kalliopi Stratigi, Evi Goulielmaki, George Niotis, Alexia Akalestou-Clocher, Katerina Gkirtzimanaki, Alexandros Zafeiropoulos, Janine Altmueller, Pantelis Topalis, George A. Garinis
Summary: DNA damage-induced R-loops contribute to the accumulation of single-stranded DNAs in the cytoplasm, triggering an immune response in the pancreata. Researchers developed an extracellular vesicle-based strategy to deliver nucleases and alleviate chronic inflammation.
Article
Cell Biology
Esther Marchena-Cruz, Lola P. Camino, Jay Bhandari, Sonia Silva, Jose Javier Marqueta-Gracia, Shahad A. Amdeen, Cristina Guillen-Mendoza, Maria L. Garcia-Rubio, Jose M. Calderon-Montano, Xiaoyu Xue, Rosa Luna, Andres Aguilera
Summary: Unscheduled R loops can lead to genome instability, a characteristic of cancer cells. By targeting activation-induced cytidine deaminase (AID), 59 potential candidates causing R loops were identified, which are enriched in factors involved in chromatin, transcription, RNA biogenesis, and other processes. The study suggests that various gene dysfunctions can affect R-loop homeostasis through different mechanisms, thereby altering cell physiology.
Review
Biochemistry & Molecular Biology
Veronica Marabitti, Pasquale Valenzisi, Giorgia Lillo, Eva Malacaria, Valentina Palermo, Pietro Pichierri, Annapaola Franchitto
Summary: Maintenance of genome stability is crucial for cell survival, which relies on accurate DNA replication. Transcription poses as a major threat to DNA replication, as collisions between the two processes occur frequently. R-loops, which consist of a DNA-RNA hybrid and displaced single-stranded DNA, are the main harmful structures associated with transcription. When their homeostasis is disturbed, R-loops become a potent source of replication stress and genome instability, leading to various human diseases including cancer. Cells have evolved multiple mechanisms to combat the deleterious consequences of R-loop persistence, and several replication fork protection factors have been implicated in preventing/removing these harmful structures.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Ioannis Karakasiliotis, Nefeli Lagopati, Konstantinos Evangelou, Vassilis G. Gorgoulis
Summary: In-depth analysis of SARS-CoV-2 biology and pathogenesis has revealed the mechanisms through which the virus induces COVID-19 pathology. Cellular senescence, linked to SARS-CoV-2 infection, may contribute to virus mutagenesis through the action of RNA-editing enzymes like APOBEC. Understanding this mechanism of virus evolution highlights the importance of inhibiting cellular senescence in SARS-CoV-2 clinical treatment.
Editorial Material
Endocrinology & Metabolism
Jedrzej Chrzanowski, Szymon Grabia, Arkadiusz Michalak, Anna Wielgus, Julia Wykrota, Beata Mianowska, Agnieszka Szadkowska, Wojciech Fendler
Article
Biochemistry & Molecular Biology
Despoina D. Gianniou, Aimilia D. Sklirou, Maria-Alexandra Papadimitriou, Katerina-Marina Pilala, Konstantinos Stravodimos, Margaritis Avgeris, Andreas Scorilas, Ioannis P. Trougakos
Summary: This study investigated the expression and role of HSPB2 and HSPB3 genes in bladder cancer patients and bladder cancer cells. The results showed increased expression levels of HSPB2 and HSPB3 genes and proteins in high-grade bladder cancer cells. In clinical samples, the expression levels of HSPB2 and HSPB3 genes were significantly downregulated in bladder tumors but showed an upregulation trend in muscle-invasive and high-grade tumors. These findings suggest that HSPB2 and HSPB3 have a pro-survival role in advanced bladder cancer and can be targeted as novel molecular markers for treatment optimization.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Anna Pula, Pawel Robak, Dariusz Jarych, Damian Mikulski, Malgorzata Misiewicz, Izabela Drozdz, Wojciech Fendler, Janusz Szemraj, Tadeusz Robak
Summary: This study aimed to analyze the expression of selected miRNAs in the serum of MM patients treated with bortezomib-based regimens and determine their ability to predict early mortality. Two miRNAs, hsa-miR-328-3p and hsa-miR-409-3p, were significantly downregulated in the early mortality group. Logistic regression analysis showed that the final model, including these miRNAs, age, and R-ISS 3, had high sensitivity and specificity in predicting early mortality.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Hematology
Santhi Devasundaram, Evangelos Terpos, Margherita Rosati, Ioannis Ntanasis-Stathopoulos, Jenifer Bear, Robert Burns, Stamatia Skourti, Panagiotis Malandrakis, Ioannis P. Trougakos, Meletios-Athanasios Dimopoulos, George N. Pavlakis, Barbara K. Felber
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Nikolaos I. Vlachogiannis, Panagiotis A. Ntouros, Maria Pappa, Evrydiki Kravvariti, Evangelia Georgia Kostaki, Georgios E. Fragoulis, Christina Papanikolaou, Dimitra Mavroeidi, Vasiliki-Kalliopi Bournia, Stylianos Panopoulos, Katerina Laskari, Aikaterini Arida, Vassilis G. Gorgoulis, Maria G. Tektonidou, Dimitrios Paraskevis, Petros P. Sfikakis, Vassilis L. Souliotis
Summary: Aging is characterized by the progressive deregulation of homeostatic mechanisms causing the accumulation of macromolecular damage, affecting organ function and leading to chronic diseases. In this study, the relationship between chronological age and DNA damage response (DDR) signals in peripheral blood mononuclear cells (PBMCs) from healthy individuals was investigated. The results showed that DNA damage levels in PBMCs were only marginally correlated with age until 50 years, but a linear relationship was observed after 50 years. Furthermore, individuals older than 50 years exhibited higher levels of endogenous double-strand breaks (DSBs), oxidative stress, apurinic/apyrimidinic sites, and decreased DSBs repair capacity compared to those younger than 50 years. Prospective studies are needed to confirm DNA damage accumulation as a biomarker of aging and determine the relevant age threshold.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Marcin Miszczyk, Lukasz Magrowski, Tomasz Krzysztofiak, Rafak Stando, Wojciech Majewski, Konrad Stawiski, Oliwia Masri, Jakub Ciepal, Gabriela Depowska, Krystyna Chimiak, Gabriela Bylica, Barbara Czapla, Makgorzata Masri, Franciszek Cichur, Iwona Jabkonska, Marta Gmerek, Zuzanna Nowicka, Piotr Wojcieszek, Jacek Sadowski, Rafak Suwinski, Pawel Rajwa, Gregor Goldner, Matthias Moll
Summary: This study aimed to determine whether BT boost was associated with a statistically significant improvement in survival and a reduction of distant metastases based on real-world data. The results showed a strong positive association between BTB and overall survival, freedom from distant metastases, and metastases-free survival in PCa patients.
RADIOTHERAPY AND ONCOLOGY
(2023)
Article
Cell Biology
Angelos Papaspyropoulos, Orsalia Hazapis, Abdullah Altulea, Aikaterini Polyzou, Panayotis Verginis, Konstantinos Evangelou, Maria Fousteri, Argyris Papantonis, Marco Demaria, Vassilis Gorgoulis
Summary: Cellular senescence is a process of irreversible cell growth arrest, accompanied by macromolecular damage and metabolic changes. Different senescence types, such as replicative, stress-induced, and oncogene-induced senescence, have been identified based on the initiating stimulus. However, it is still unknown whether reduced protein synthesis, a hallmark of senescence, is applicable to different senescence subtypes and if distinct molecular mechanisms are involved.
Editorial Material
Biochemistry & Molecular Biology
Giorgos Theocharous, Angelos Papaspyropoulos, Vassilis Gorgoulis
Review
Oncology
Konstantinos Evangelou, Konstantinos Belogiannis, Angelos Papaspyropoulos, Russell Petty, Vassilis G. Gorgoulis
Summary: Cellular senescence is a stress response mechanism that results from various stimuli. Senescent cells exhibit cell-cycle arrest and altered function. Recent evidence in cancer research has introduced the concept of escape-from-senescence, where under certain conditions, senescent cells may resume proliferation with highly aggressive features. This has implications for pathology and therapy, suggesting the need for personalized approaches and the inclusion of senolytic agents in conventional cancer treatments.
JOURNAL OF PATHOLOGY
(2023)
Article
Oncology
Zuzanna Nowicka, Bartlomiej Tomasik, David Kozono, Konrad Stawiski, Thomas Johnson, Daphne Haas-Kogan, Marek Ussowicz, Dipanjan Chowdhury, Wojciech Fendler
Summary: The study demonstrates that serum miRNAs can be used as functional biodosimeters to predict the biological impact of radiation doses in humans undergoing total body irradiation. A logistic regression model was built using miR-150-5p, miR-30b-5p, and miR-320c, which showed high accuracy in identifying samples drawn after irradiation.
RADIOTHERAPY AND ONCOLOGY
(2023)
Article
Oncology
Jakub Malinowski, Wioletta Pietruszewska, Konrad Stawiski, Magdalena Kowalczyk, Magda Baranska, Aleksander Rycerz, Ewa Niebudek-Bogusz
Summary: The standard protocol for distinguishing between benign and malignant lesions remains clinical judgment and histopathological confirmation. High-speed videoendoscopy (HSV) can accurately assess the vibratory characteristics of vocal folds. Machine learning models based on HSV analysis could potentially indicate a heightened risk of cancerous mass, aiding in early cancer detection, but further investigation and validation is needed.
Article
Biochemical Research Methods
Bara A. Badwan, Gerry Liaropoulos, Efthymios Kyrodimos, Dimitrios Skaltsas, Aristotelis Tsirigos, Vassilis G. Gorgoulis
Summary: In recent years, there has been increasing interest in using machine learning algorithms (MLAs) in oncology for various biomedical applications. MLAs have the potential to provide valuable insights and predictions by representing both the disease state and therapeutic agents. This perspective paper lays out approaches to effectively utilize MLAs in oncology by representing both the disease state and therapeutic agents, leading to novel insights and relevant predictions.
CELL REPORTS METHODS
(2023)
Article
Oncology
Anna Pula, Tadeusz Robak, Izabela Drozdz, Konrad Stawiski, Aleksander Rycerz, Malgorzata Misiewicz, Pawel Robak
Summary: This study aimed to develop a prognostic model for bortezomib resistance in multiple myeloma (MM) based on miRNA expression profiling. The results showed that upregulated miR-27b-3p and let-7b-5p were associated with bortezomib resistance in previously untreated MM patients. These miRNAs may serve as biomarkers of treatment response in MM.
LEUKEMIA & LYMPHOMA
(2023)