Article
Cell Biology
Amandine Bery, Olivier Etienne, Laura Mouton, Sofiane Mokrani, Christine Granotier-Beckers, Laurent R. Gauthier, Justyne Feat-Vetel, Thierry Kortulewski, Elodie A. Peres, Chantal Desmaze, Philippe Lestaveal, Vilma Barroca, Antony Laugeray, Fawzi Boumezbeur, Vincent Abramovski, Stephane Mortaud, Arnaud Menuet, Denis Le Bihan, Jean-Pierre de Villartay, Francois D. Boussin
Summary: XLF/Cernunnos is a crucial component of the ligation complex involved in cNHEJ, a DNA repair pathway. In Xlf-/- mice, neurodevelopmental delays, behavioral alterations, microcephaly, and apoptosis of neural cells are observed, resembling clinical features in humans deficient in cNHEJ. Premature neurogenesis in these mice is caused by asymmetric chromosome segregation, suggesting a link between chromosome dynamics and neurodevelopmental pathologies associated with NHEJ deficiency or genotoxic stress.
Article
Genetics & Heredity
Xueping Gu, Qinjin Dai, Peng Du, Ning Li, Jiahui Li, Simiao Zeng, Shuyi Peng, Shengjun Tang, Lei Wang, Zhongcheng Zhou
Summary: Pol delta plays a crucial role in DNA replication and damage repair. Pold4, the smallest subunit of Pol delta, is degraded in response to DNA damage or in S-phase. The exact contribution of Pold4 in mammals is still unclear, but it seems to be dispensable for normal cell processes. Pold4 knockout mice show no pathological changes and have increased longevity. This suggests that Pold4 could be a potential target for lung cancer therapy, as its absence does not affect normal cells but does impact cancer cells.
Article
Biochemistry & Molecular Biology
Zida Zhu, Taisuke Kitano, Masami Morimatsu, Arisa Tanaka, Ryo Morioka, Xianghui Lin, Koichi Orino, Yasunaga Yoshikawa
Summary: In this study, we found that the expression of BRCA2 CTRBD protein enhances the resistance of cells to X-ray irradiation and mitomycin C by increasing homologous recombination efficiency for DNA repair. This finding provides a new approach for protecting cells against the damage caused by radiation therapy and chemotherapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Chiara Chiozzini, Francesco Manfredi, Flavia Ferrantelli, Patrizia Leone, Andrea Giovannelli, Eleonora Olivetta, Maurizio Federico
Summary: The study found that the C-terminal deletion of Nef(mut) retains its ability to anchor with EVs and maintain immunogenicity, making it a potentially safer alternative for human vaccines.
Article
Biochemistry & Molecular Biology
Raquel Gago-Fuentes, Valentyn Oksenych
Summary: NHEJ factors XLF, DNA-PKcs, and PAXX play crucial roles in maintaining neural stem and progenitor cell populations and neurodevelopment in mammals, particularly evident in double knockout models.
Article
Multidisciplinary Sciences
Metztli Cisneros-Aguirre, Felicia Wednesday Lopezcolorado, Linda Jillianne Tsai, Ragini Bhargava, Jeremy M. Stark
Summary: DNAPKcs is required for blunt DNA break end joining when XLF is weakened, but its influence is not enhanced with loss of XLF for homologous recombination and radiation resistance.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Desiree Boeck, Tanja Rothgangl, Lukas Villiger, Lukas Schmidheini, Mai Matsushita, Nicolas Mathis, Eleonora Ioannidi, Nicole Rimann, Hiu Man Grisch-Chan, Susanne Kreutzer, Zacharias Kontarakis, Manfred Kopf, Beat Thoeny, Gerald Schwank
Summary: Prime editing is a highly versatile CRISPR-based technology that is able to edit genomes without causing DNA double-strand breaks. In this study, the researchers developed a smaller version of the SpCas9 prime editor and used a viral delivery system to edit genes in the liver. They were able to successfully correct a disease-causing mutation in a mouse model of phenylketonuria, leading to therapeutic reduction of phenylalanine in the blood. Although there are limitations to the current approach, further development of the technology may offer potential treatments for genetic liver diseases.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Cell Biology
Foon Wu-Baer, Madeline Wong, Lydia Tschoe, Chyuan-Sheng Lin, Wenxia Jiang, Shan Zha, Richard Baer
Summary: Homology-directed repair (HDR) of double-strand DNA breaks (DSBs) relies on the enzymatic resection of DNA ends by CtIP/Sae2 protein, with ATM/ATR phosphorylation enhancing DNA resection but not essential for animal development.
Article
Genetics & Heredity
Qumar Zaman, Ranjha Khan, Uzma Hameed, Wasim Shah, Ahmed Waqas, Muhammad Zubair, Sobia Dil, Tuba Zafar, Asim Ali, Ahsanullah Unar, Qinghua Shi
Summary: The study found that Exo5 knockout mice are fertile despite a slight decrease in sperm count, and showed no remarkable differences in epididymal histology and testis/body weight ratio. Under normal breeding conditions, Exo5 seems to have no essential role in spermatogenesis in mice.
Article
Oncology
Atsushi Tanaka, Koutarou Nishimura, Wataru Saika, Ayana Kon, Yui Koike, Hiromi Tatsumi, June Takeda, Masaki Nomura, Weijia Zang, Manabu Nakayama, Masashi Matsuda, Hiromi Yamazaki, Miki Fukumoto, Hiromi Ito, Yasutaka Hayashi, Toshio Kitamura, Hiroshi Kawamoto, Akifumi Takaori-Kondo, Haruhiko Koseki, Seishi Ogawa, Daichi Inoue
Summary: SETBP1 is a potential epigenetic regulator involved in myeloid malignancies with poor prognosis. Although mutations in SETBP1 are recurrently detected in these malignancies, its role in normal hematopoiesis is poorly understood. This study found that depletion of SETBP1 in normal hematopoiesis had minimal effects on cell functions, suggesting its dispensable role in normal development. Unexpectedly, despite its association with poor outcomes in AML, SETBP1 was found to be dispensable for the development or maintenance of AML. This highlights the concept that a nonessential gene can act as an oncogene when the protein degradation machinery is damaged.
Article
Biochemistry & Molecular Biology
Eline Pottie, Jolien Storme, Christophe P. Stove
Summary: This study used NanoBiT functional complementation assay to investigate the recruitment of beta-arrestins upon activation of the P2Y(2) receptor. The results suggest that the C-terminal tail plays a role in modulating the interaction with beta-arrestins.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Ning Kon, Michael Churchill, Huan Li, Siddhartha Mukherjee, James J. Manfredi, Wei Gu
Summary: The study highlights the essential role of robust p53 stabilization in acute p53 responses such as DNA damage, while also emphasizing that low basal levels of p53 protein are crucial for p53 activation and tumor suppression.
Article
Biochemistry & Molecular Biology
Garrett M. Warren, Juncheng Wang, Dinshaw J. Patel, Stewart Shuman
Summary: Mycobacterium smegmatis Lhr and Escherichia coli Lhr are novel bacterial helicases with ATPase, translocase, and ATP-dependent helicase activities, characterized by their ability to translocate on ssDNA and unwind secondary structures, with a preference for RNA:DNA hybrid. Their complex quaternary structures and functional domains contribute to their unique enzymatic properties.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Zhihao Wang, Zhicheng Pan, Samir Adhikari, Bryan T. Harada, Lei Shen, Wei Yuan, Tharindumala Abeywardana, Qais Al-Hadid, Jeremy M. Stark, Chuan He, Lan Lin, Yanzhong Yang
Summary: The research reveals that arginine methylation of METTL14 is a novel pathway controlling m(6)A deposition in mammalian cells, with deficiency in this methylation leading to significantly reduced global m(6)A levels in mESCs. These findings highlight the importance of arginine methylation in RNA metabolism and its impact on various cellular processes, including stem cell maintenance and DNA repair.
Article
Cell Biology
Huaping Xiao, Fanghua Li, Emil Mladenov, Aashish Soni, Veronika Mladenova, Bing Pan, Rositsa Dueva, Martin Stuschke, Beate Timmermann, George Iliakis
Summary: The load of DNA double-strand breaks induced by ionizing radiation plays a key role in determining the repair pathway choice in higher eukaryotes. The integration of DNA-PKcs into resection regulation suggests a mechanism adaptively facilitating resection. Mutations in DNA-PKcs result in hyper-resection, ruling out the competition between c-NHEJ and HR as the cause of increased resection.
Article
Biology
Benoit Roch, Vincent Abramowski, Olivier Etienne, Stefania Musilli, Pierre David, Jean-Baptiste Charbonnier, Isabelle Callebaut, Francois D. Boussin, Jean-Pierre de Villartay
Summary: The development of a new Xrcc4(M61R) separation of function mouse line demonstrated the importance of XRCC4 in stabilizing DNA ligase IV in V(D)J recombination. Functional interplays between XRCC4 and PAXX, ATM, and Xlf were identified, with significant impacts on mouse immune system development. These findings provide new insights into the clinical manifestations of human XRCC4-deficient condition.
Article
Hematology
Laetitia Kermasson, Dmitri Churikov, Aya Awad, Riham Smoom, Elodie Lainey, Fabien Touzot, Severine Audebert-Bellanger, Sophie Haro, Laureline Roger, Emilia Costa, Maload Mouf, Adriana Bottero, Matias Oleastro, Chrystelle Abdo, Jean-Pierre De Villartay, Vincent Geli, Yehuda Tzfati, Isabelle Callebaut, Silvia Danielian, Gabriela Soares, Caroline Kannengiesser, Patrick Revy
Summary: Inherited bone marrow failure syndromes (IBMFSs) are a group of disorders characterized by impaired production of blood cells. This study identifies biallelic variants in the Apollo gene as a genetic cause of a severe IBMFS that combines clinical hallmarks of dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome. The findings highlight the importance of Apollo in genome maintenance and expand our understanding of IBMFSs.
Article
Respiratory System
Effrosyni D. Manali, Caroline Kannengiesser, Raphael Borie, Ibrahima Ba, Demosthenes Bouros, Aikaterini Markopoulou, Katerina Antoniou, Lykourgos Kolilekas, Andriana I. Papaioannou, Vasileios Tzilas, Argyrios Tzouvelekis, Zoe Daniil, Evangelia Fouka, Despoina Papakosta, Areti Xyfteri, Anna Karakatsani, Stylianos Loukides, Ioanna Korbila, Ioannis P. Tomos, Athanasios K. Konstantinidis, Athina Gogali, Paschalis Steiropoulos, Ilias C. Papanikolaou, Chrysa Bazaka, Aggeliki Haritou, Theodoros Vassilakopoulos, Maria Maniati, Konstantinos Kagouridis, Evangelos Markozannes, Evangelos Bouros, Christina Rampiadou, Georgia Kounti, Athina Trachalaki, Ilias Dimeas, Theodoros Karampitsakos, Panagiotis Lyberopoulos, Nikolaos Malamadakis, Sofia Spyropoulou, Patrick Revy, Elodie Lainey, Philippe Dieude, Khedidja Rebah, Christelle Menard, Claire Oudin, Cecile Masson, Aurelie Plessier, Marie Legendre, Nadia Nathan, Aurore Coulomb-L'Hermine, Annick Clement, Serge Amselem, Catherine Boileau, Bruno Crestani, Spyros Papiris
Summary: This French-Greek collaborative study aimed to investigate the genetic components and characteristics of Greek IPF patients with suspected heritability. The study identified associations between the MUC5B rs35705950 T risk allele, TRG pathogenic variations, and prognosis in IPF patients.
Article
Cell Biology
Romain Donne, Maeva Saroul-Ainama, Pierre Cordier, Adel Hammoutene, Christelle Kabore, Mira Stadler, Ivan Nemazanyy, Isabelle Galy-Fauroux, Mounia Herrag, Tobias Riedl, Marie Chansel-Da Cruz, Stefano Caruso, Stephanie Bonnafous, Rupert Ollinger, Roland Rad, Kristian Unger, Albert Tran, Jean-Pierre Couty, Philippe Gual, Valerie Paradis, Severine Celton-Morizur, Mathias Heikenwalder, Patrick Revy, Chantal Desdouets
Summary: This study investigated the mechanisms of DNA damage response during NAFLD and found that nucleotide pool imbalance is the key driver of replication stress (RS), and DNA damage also activates the cGAS/STING pathway, promoting disease progression.
DEVELOPMENTAL CELL
(2022)
Review
Allergy
Benjamin Fournier, Nizar Mahlaoui, Despina Moshous, Jean-Pierre De Villartay
Summary: Several primary immunodeficiencies are caused by defects in the general DNA repair machinery, leading to genome instability and increased susceptibility to malignancies. It is crucial to assess the functionality of the DNA repair apparatus before genotoxic treatment when the molecular cause of the disease is unknown.
PEDIATRIC ALLERGY AND IMMUNOLOGY
(2022)
Article
Immunology
Maria Chiriaco, Giorgiana Madalina Ursu, Donato Amodio, Nicola Cotugno, Stefano Volpi, Francesco Berardinelli, Simone Pizzi, Cristina Cifaldi, Matteo Zoccolillo, Ignazia Prigione, Silvia Di Cesare, Carmela Giancotta, Elisa Anastasio, Beatrice Rivalta, Lucia Pacillo, Paola Zangari, Alessandro G. Fiocchi, Andrea Diociaiuti, Alessandro Bruselles, Francesca Pantaleoni, Andrea Ciolfi, Valentina D'Oria, Giuseppe Palumbo, Marco Gattorno, Maya El Hachem, Jean-Pierre de Villartay, Andrea Finocchi, Paolo Palma, Paolo Rossi, Marco Tartaglia, Alessandro Aiuti, Antonio Antoccia, Gigliola Di Matteo, Caterina Cancrini
Summary: ARPC1B deficiency is an inborn error of immunity characterized by combined immunodeficiency and recurrent infections. A recent study found that ARPC1B-deficient patients also exhibit increased radiosensitivity, suggesting it may be an additional trait of the disease. These findings have important implications for the clinical management and treatment interventions for ARPC1B-deficient patients.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Pascal Chappert, Francois Huetz, Marie-Alix Espinasse, Fabrice Chatonnet, Louise Pannetier, Lucie Da Silva, Clara Goetz, Jerome Megret, Aurelien Sokal, Etienne Crickx, Ivan Nemazanyy, Vincent Jung, Chiara Guerrera, Sebastien Storck, Matthieu Mahevas, Antonio Cosma, Patrick Revy, Thierry Fest, Claude-Agnes Reynaud, Jean-Claude Weill
Summary: This study identifies the mechanisms that contribute to the long-term survival of memory B cells, including early telomere elongation, affinity selection, and access to a specific niche.
Article
Immunology
Vincent Allain, Virginie Grandin, Veronique Meignin, Remi Bertinchamp, David Boutboul, Claire Fieschi, Lionel Galicier, Laurence Gerard, Marion Malphettes, Jacinta Bustamante, Mathieu Fusaro, Nathalie Lambert, Jeremie Rosain, Christelle Lenoir, Sven Kracker, Frederic Rieux-Laucat, Sylvain Latour, Jean-Pierre De Villartay, Capucine Picard, Eric Oksenhendler
Summary: This study found that lymphoma may be a revealing symptom of an underlying primary immunodeficiency in patients with hypogammaglobulinemia, challenging the distinction between primary and secondary hypogammaglobulinemia. The occurrence of Hodgkin lymphoma was more common prior to the diagnosis of hypogammaglobulinemia, while MALT lymphoma was absent. Genetic analysis identified a molecular diagnosis in some patients, with a significant portion presenting with late-onset combined immunodeficiency.
JOURNAL OF CLINICAL IMMUNOLOGY
(2023)
Review
Genetics & Heredity
Patrick Revy, Caroline Kannengiesser, Alison A. Bertuch
Summary: This article reviews the confirmed and potential genes causing telomere diseases and describes their main functions in telomere biology. The authors also discuss the genetic features underlying the complexity of these diseases.
NATURE REVIEWS GENETICS
(2023)
Article
Multidisciplinary Sciences
Panagiotis Antoniou, Giulia Hardouin, Pierre Martinucci, Giacomo Frati, Tristan Felix, Anne Chalumeau, Letizia Fontana, Jeanne Martin, Cecile Masson, Megane Brusson, Giulia Maule, Marion Rosello, Carine Giovannangeli, Vincent Abramowski, Jean-Pierre De Villartay, Jean-Paul Concordet, Filippo Del Bene, Wassim El Nemer, Mario Amendola, Marina Cavazzana, Anna Cereseto, Oriana Romano, Annarita Miccio
Summary: Sickle cell disease and beta-thalassemia can be treated by editing the HBG promoters to induce gamma-globin expression. This approach is safe and leads to reactivation of fetal hemoglobin and rescue of the pathological phenotype in patient hematopoietic stem/progenitor cells. Creating a binding site for the KLF1 activator is the most potent strategy.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Jean Pierre de Villartay, Emmanuelle Pannier, Jeanne Sibiude, Pierre Frange, Roland Tubiana, Stephane Blanche
Summary: The effectiveness of anti-HIV drugs in preventing perinatal transmission has been confirmed. It is crucial to evaluate the tolerability of drug exposure during pregnancy due to the number of exposed children. Similarity in the structure of HIV integrase and recombinase-activating gene enzyme suggests potential inhibition of recombinase-activating gene by anti-integrases. Our study found that in utero exposure to raltegravir did not impact the T-lymphocyte repertoire in 12 newborns, providing reassuring data that should be verified for other anti-integrases.
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
(2023)
Letter
Oncology
Jean Galtier, Sophie Dimicoli-Salazar, Aurelien Trimouille, Elodie Lainey, Patrick Revy, Audrey Bidet, Yoann Vial, Edouard Forcade, Marie-Laure Negrier-Leibreich, Etienne Riviere, Julie Tinat, Nathalie Le Meur, Christelle Menard, Arnaud Pigneux, Thibaut Leguay, Pierre-Yves Dumas, Ba Ibrahima, Caroline Kannengiesser
LEUKEMIA & LYMPHOMA
(2023)
Article
Allergy
Annaise J. Jauch, Olivier Bignucolo, Sayuri Seki, Marie Ghraichy, Ottavia M. Delmonte, Valentin von Niederhausern, Rebecca Higgins, Adhideb Ghosh, Masako Nishizawa, Mariko Tanaka, Adrian Baldrich, Julius Koppen, Julia R. Hirsiger, Robin Hupfer, Stephan Ehl, Anne Rensing-Ehl, Helmut Hopfer, Spasenija Savic Prince, Stephen R. Daley, Florian A. Marquardsen, Benedikt J. Meyer, Michael Tamm, Thomas D. Daikeler, Tamara Diesch, Thomas Kuehne, Arthur Helbling, Caroline Berkemeier, Ingmar Heijnen, Alexander A. Navarini, Johannes Truck, Jean-Pierre de Villartay, Annette Oxenius, Christoph T. Berger, Christoph Hess, Luigi D. Notarangelo, Hiroyuki Yamamoto, Mike Recher
Summary: This study reveals that monoallelic LIG4 mutations may lead to immune dysregulation in humans, characterized by autoimmune cytopenias, lymphoproliferation, decreased specific T cells, and DNA damage intolerance. This finding is important for understanding the pathogenesis of immune-related disorders.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
Article
Hematology
Richa Sharma, Sushree S. Sahoo, Masayoshi Honda, Sophie L. Granger, Charnise Goodings, Louis Sanchez, Axel Kunstner, Hauke Busch, Fabian Beier, Shondra M. Pruett-Miller, Marcus B. Valentine, Alfonso G. Fernandez, Ti-Cheng Chang, Vincent Geli, Dmitri Churikov, Sandrine Hirschi, Victor B. Pastor, Melanie Boerries, Melchior Lauten, Charikleia Kelaidi, Megan A. Cooper, Sarah Nicholas, Jill A. Rosenfeld, Sophia Polychronopoulou, Caroline Kannengiesser, Carole Saintome, Charlotte M. Niemeyer, Patrick Revy, Marc S. Wold, Maria Spies, Miriam Erlacher, Stephane Coulon, Marcin W. Wlodarski
Summary: This study identifies germline RPA1 variants in patients with TBD/STS and demonstrates the functional consequences of these variants. The findings suggest that these variants enhance DNA-binding function and impair hematopoietic differentiation. Somatic genetic rescue is also observed in some patients, leading to stabilized blood counts.
