Article
Biochemistry & Molecular Biology
Laurene Sonzogni, Melanie L. Ferlazzo, Adeline Granzotto, Beatrice Fervers, Laurent Charlet, Nicolas Foray
Summary: The mechanistic model RIANS from radiobiology is crucial for understanding the recognition, repair and genotoxic stress response of DNA double-strand breaks induced by radiation. This model also applies to exposure to metal ions. Our study found that the induction of DSB by pesticides depends on their concentration and the RIANS status of cells. Impaired DSB recognition and repair, leading to toxicity, can occur when the nucleo-shuttling of ATM is delayed. Additionally, the combination of certain metal ions and pesticides can have additive or supra-additive effects on DSB recognition and/or repair.
Article
Biochemistry & Molecular Biology
Ihsan Dereli, Marcello Stanzione, Fabrizio Olmeda, Frantzeskos Papanikos, Marek Baumann, Sevgican Demir, Fabrizia Carofiglio, Julian Lange, Bernard de Massy, Willy M. Baarends, James Turner, Steffen Rulands, Attila Toth
Summary: This study elucidates that DSB restricts the DSB machinery through at least four distinct pathways, ensuring that DSBs are well-distributed and restricted to specific genomic locations and prophase stages to promote genome integrity.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Oncology
Kai Zhang, Qingnan Wu, Wenzhong Liu, Yan Wang, Lianmei Zhao, Jie Chen, Haoyu Liu, Siqi Liu, Jinting Li, Weimin Zhang, Qimin Zhan
Summary: This study identified a novel DDR regulator, FAM135B, which plays a crucial role in maintaining genomic integrity and promoting DNA repair. The results demonstrated that FAM135B can enhance homologous recombination and non-homologous end-joining repairs, as well as improve DNA damage response by physically binding to TIP60 and enhancing its activity.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Muriel Viau, Laurene Sonzogni, Melanie L. Ferlazzo, Elise Berthel, Sandrine Pereira, Larry Bodgi, Adeline Granzotto, Clement Devic, Beatrice Fervers, Laurent Charlet, Nicolas Foray
Summary: Studies suggest that metals may induce DSB through the nucleo-shuttling of ATM, affecting toxicity and carcinogenicity. The properties, concentration, and tissue type of different metals can all have an impact on this process.
Review
Cell Biology
Corinne Grey, Bernard de Massy
Summary: The axial element plays a crucial role in establishing sister chromatid cohesion and meiotic recombination during prophase I of meiosis, contributing to the successful outcome of meiosis I.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Joelle Al-Choboq, Melanie L. Ferlazzo, Laurene Sonzogni, Adeline Granzotto, Laura El-Nachef, Mira Maalouf, Elise Berthel, Nicolas Foray
Summary: Usher syndrome is a rare genetic disease characterized by hearing loss, visual impairment, and vestibular dysfunctions. This study provides the first radiobiological characterization of cells from USH1 patients at both molecular and cellular levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Eymeric Le Reun, Larry Bodgi, Adeline Granzotto, Laurene Sonzogni, Melanie L. Ferlazzo, Joelle Al-Choboq, Laura El-Nachef, Juliette Restier-Verlet, Elise Berthel, Clement Devic, Audrey Bouchet, Michel Bourguignon, Nicolas Foray
Summary: Tissue overreactions are a medical issue during or after anti-cancer radiotherapy, and predicting and preventing them is a major task for radiobiologists. While there is no consensus on the best predictor for tissue overreactions, radiation oncologists have proposed a scale to quantify the severity of these reactions. However, few studies have used this scale to evaluate the statistical robustness of predictive assays for radiosensitivity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Yang Liang, Yuefeng Qin, Guoyun Jiang, Wenli Feng, Ying Yuan
Summary: This study reveals the potential role of MDC1 in the treatment of CML and suggests it as an alternative option for IM drug resistance dilemma, by regulating the DNA damage repair mechanism.
Article
Cell Biology
Watanya Trakarnphornsombat, Hiroshi Kimura
Summary: DNA double-strand breaks (DSBs) can cause genetic mutation and histone H2AX is phosphorylated by kinases such as ATM, ATR, and DNA-PK upon DSB induction. The accumulation kinetics of ?-H2AX were similar in ATM-proficient and-deficient cells, but delayed in the presence of a DNA-PK inhibitor. Ku80 (XRCC5) diffuses freely in the nucleus, while ATM repeatedly binds to and dissociates from chromatin. ATM accumulation at damage sites is regulated by the histone acetyltransferase MOF, but does not necessarily reflect in the ?-H2AX level, suggesting distinct actions of ATM and DNA-PK in immediate ?-H2AX accumulation.
JOURNAL OF CELL SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Aaron Mendez-Bermudez, Liudmyla Lototska, Melanie Pousse, Florent Tessier, Oliver Croce, Chrysa M. Latrick, Veronica Cherdyntseva, Joe Nassour, Jiang Xiaohua, Yiming Lu, Corinne Abbadie, Sarantis Gagos, Jing Ye, Eric Gilson
Summary: Cellular senescence triggers various types of heterochromatin remodeling, including decondensation, DNA damage, and illegitimate recombination. In this study, it was discovered that at the onset of senescence, pericentromeric heterochromatin is specifically dismantled due to telomere shortening or genotoxic stress. This process is initiated by the TP53-TRF2 axis and involves the downregulation of TRF2, resulting in heterochromatin decondensation and DNA breaks.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Cell Biology
Yulia Mitiagin, Ari Barzilai
Summary: The review summarizes accumulating evidence that ataxia-telangiectasia mutated kinase is crucial for maintaining cellular homeostasis and has both nuclear and cytoplasmic functions. However, the specific functions of ataxia-telangiectasia mutated that lead to cerebellar degeneration when lost are still unknown. The review discusses the role of ataxia-telangiectasia mutated in cerebellar pathology, including its nuclear functions in DNA damage response circuits and its cytoplasmic and mitochondrial functions related to cellular homeostasis.
NEURAL REGENERATION RESEARCH
(2023)
Article
Medicine, Research & Experimental
Yue Wang, Yi-Li Feng, Qian Liu, Jing-Jing Xiao, Si-Cheng Liu, Zhi-Cheng Huang, An-Yong Xie
Summary: By studying the TREX2 3'-5' exonuclease, we found that its overexpression can enhance the efficiency of paired SpCas9n in genome editing, particularly for 3'-overhanging ends. This approach can be further simplified and made safer by fusing TREX2 with SpCas9n.
MOLECULAR THERAPY NUCLEIC ACIDS
(2023)
Article
Biology
Jean-Thomas Bachelet, Adeline Granzotto, Melanie Ferlazzo, Laurene Sonzogni, Elise Berthel, Clement Devic, Nicolas Foray
Summary: MacCune-Albright syndrome (MAS) is a rare autosomal dominant osteo-hormonal disorder characterized by severe polyostotic fibrous dysplasia, 'cafe-au-lait' pigmentation, and multiple endocrinopathies. MAS is caused by somatic mutations in the GNAS gene and is associated with radiation-induced malignant tumors. Bisphosphonates treatment has been shown to improve outcomes for MAS patients by increasing bone density. The study found that MAS cells exhibit moderate but significant radiosensitivity, potentially due to impaired DNA repair and signaling pathways. Further research is needed to explore the clinical application of bisphosphonates and statins in MAS treatment, and to assess potential risks associated with radiation exposure.
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
(2021)
Article
Cell Biology
Elise Berthel, Laurent Pujo-Menjouet, Eymeric Le Reun, Laurene Sonzogni, Joelle Al-Choboq, Abdennasser Chekroun, Adeline Granzotto, Clement Devic, Melanie L. Ferlazzo, Sandrine Pereira, Michel Bourguignon, Nicolas Foray
Summary: Alzheimer's disease (AD) is a common neurodegenerative dementia, and its molecular origins, genetic predisposition, and therapeutic approach are still debated. It has been found that cells from AD patients are sensitive to ionizing radiation, and a new model suggests that the ATM-dependent DNA double-strand breaks signaling and repair may play a role in the aging process. These findings provide insights into the understanding and early diagnosis of AD.
Article
Cell Biology
Md Akram Hossain, Yunfeng Lin, Garrett Driscoll, Jia Li, Anne McMahon, Joshua Matos, Haichao Zhao, Daisuke Tsuchimoto, Yusaku Nakabeppu, Jianjun Zhao, Shan Yan
Summary: APE2 is essential for activating the ATR DDR pathway in response to various stressful conditions in Xenopus laevis egg extracts and human pancreatic cancer cells. Inhibition of APE2 leads to increased DNA damage and sensitizes cancer cells to chemotherapy drugs, indicating its crucial role in maintaining genome integrity.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Katerina Duskova, Pauline Lejault, Elie Benchimol, Regis Guillot, Sebastien Britton, Anton Granzhan, David Monchaud
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2020)
Article
Biochemical Research Methods
Regine Janel-Bintz, Lauriane Kuhn, Philippe Frit, Johana Chicher, Jerome Wagner, Lajos Haracska, Philippe Hammann, Agnes M. Cordonnier
Article
Biochemistry & Molecular Biology
Joanna Zell, Katerina Duskova, Leila Chouh, Madeleine Bossaert, Nicolas Cheron, Anton Granzhan, Sebastien Britton, David Monchaud
Summary: DNA is a dynamic molecule that can fold into alternative higher-order structures like G-quadruplexes (G4s) and three-way DNA junctions (TWJs). Ligands targeting both TWJs and G4s in vitro show distinct cellular effects, suggesting a pivotal role of TWJs in cells. These dual TWJ-/G4-ligands can be combined with DDR inhibitors for an efficient synthetic lethality strategy.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Abhishek Bharadwaj Sharma, Helene Erasimus, Lia Pinto, Marie-Christine Caron, Diyavarshini Gopaul, Thibaut Peterlini, Katrin Neumann, Petr Nazarov, Sabrina Fritah, Barbara Klink, Christel C. Herold-Mende, Simone P. Niclou, Philippe Pasero, Patrick Calsou, Jean-Yves Masson, Sebastien Britton, Eric Van Dyck
Summary: In this study, XAB2 was identified as a factor required for resistance to seDSBs induced by the chemotherapeutic drug temozolomide, and it prevents Ku retention and abortive HR at seDSBs induced by temozolomide and camptothecin through a pathway operating parallel to the ATM-CtIP-MRE11 axis. XAB2 depletion results in unproductive RAD51-ssDNA associations, leading to increased NHEJ engagement and genetic instability in S/G2.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
A. Pipier, A. Devaux, T. Lavergne, A. Adrait, Y. Coute, S. Britton, P. Calsou, J. F. Riou, E. Defrancq, D. Gomez
Summary: G-quadruplexes (G4) are non-canonical secondary structures with intrinsic polymorphic nature; their functions in cells rely on protein or enzymatic factors; constrained G4 structures are biomolecular objects used to determine the topology preferences of known G4-interacting factors.
SCIENTIFIC REPORTS
(2021)
Article
Biology
Madeleine Bossaert, Angelique Pipier, Jean-Francois Riou, Celine Noirot, Linh-Trang Nguyen, Remy-Felix Serre, Olivier Bouchez, Eric Defrancq, Patrick Calsou, Sebastien Britton, Dennis Gomez
Summary: Through an unbiased genetic approach, the study identified TOP2A as a major effector of cytotoxicity induced by G4 ligands. The study shows that both TOP2 activity and transcription play crucial roles in DNA break production following G4 ligand treatments. In contrast, the clastogenic activity of G4 ligands is counteracted by TOP1 and factors promoting transcriptional elongation.
Article
Cell Biology
Carine Racca, Sebastien Britton, Sabrine Hedouin, Claire Francastel, Patrick Calsou, Florence Larminat
Summary: Centromeres, defined by chromatin containing CENP-A, play a crucial role in chromosome inheritance and genome stability. BRCA1 associates with centromeres to counteract R-loop accumulation at centromeric alpha-satellite repeats, maintaining centromere stability and identity.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Ikrame Lazar, Bertrand Fabre, Yongmei Feng, Ali Khateb, Philippe Frit, Anna Kashina, Tongwu Zhang, Emily Avitan-Hersh, Hyungsoo Kim, Kevin Brown, Ivan Topisirovic, Ze'ev A. Ronai
Summary: ATE1 is overexpressed in NRAS-mutant melanomas and downregulated in BRAF-mutant melanomas. Decreased ATE1 expression reduces the aggressiveness of melanoma cells and affects their response to drugs and serum deprivation. ATE1 may play a role in regulating the function of AXIN1 in melanoma.
Article
Biology
Pascal Demange, Etienne Joly, Julien Marcoux, Patrick R. A. Zanon, Dymytrii Listunov, Pauline Rulliere, Cecile Barthes, Celine Noirot, Jean-Baptiste Izquierdo, Alexandrine Rozie, Karen Pradines, Romain Hee, Maria Vieira de Brito, Marlene Marcellin, Remy-Felix Serre, Olivier Bouchez, Odile Burlet-Schiltz, Maria Conceicao Ferreira Oliveira, Stephanie Ballereau, Vania Bernardes-Genisson, Valerie Maraval, Patrick Calsou, Stephan M. Hacker, Yves Genisson, Remi Chauvin, Sebastien Britton
Summary: The enantiospecific cytotoxicity of several terminal alkynylcarbinols, including highly cytotoxic dialkynylcarbinols, involves a bioactivation by HSD17B11. The bioactivated dialkynylcarbinols modify proteins involved in protein-quality control mechanisms, leading to cell death and potential therapeutic applications in cancer treatment.
Article
Multidisciplinary Sciences
Murielle Seif-El-Dahan, Antonia Kefala-Stavridi, Philippe Frit, Steven W. Hardwick, Dima Y. Chirgadze, Taiana Maia De Oliviera, Sebastien Britton, Nadia Barboule, Madeleine Bossaert, Arun Prasad Pandurangan, Katheryn Meek, Tom L. Blundell, Virginie Ropars, Patrick Calsou, Jean -Baptiste Charbonnier, Amanda K. Chaplin
Summary: This research investigates the structural and functional role of the accessory protein PAXX in nonhomologous end joining, a critical mechanism for repairing DNA double-strand breaks. The study reveals that PAXX can bind to Ku70/80 and two alternate forms of DNA-PK dimers, acting as a structural bridge. Engagement of both PAXX and XLF provides a complementary advantage for DNA end synapsis and end joining in cells.
Review
Biochemistry & Molecular Biology
Joanna Zell, Francesco Rota Sperti, Sebastien Britton, David Monchaud
Summary: Damaging DNA is an effective strategy to combat cancer cell proliferation through the DNA damage response (DDR), which is crucial for optimizing chemotherapeutic DNA targeting. New research has identified promising therapeutic targets and approaches, highlighting a highly promising chemotheutic strategy that combines enhanced-specificity DNA damaging and DDR targeting agents. The study emphasizes significant scientific advances achieved through multidisciplinary research efforts in chemical biology.
RSC CHEMICAL BIOLOGY
(2021)
