Article
Biochemistry & Molecular Biology
Sapir Schlam-Babayov, Ariel Bensimon, Michal Harel, Tamar Geiger, Ruedi Aebersold, Yael Ziv, Yosef Shiloh
Summary: This study conducted a comprehensive phosphoproteomic analysis in human wild-type and A-T cells to reveal the fine-tuned dynamics and relationships between PIKKs in the response to genotoxic stress. The results highlight the complex interactions among ATM, ATR, and DNA-PK in the DDR.
Article
Plant Sciences
Fabienne Gehrke, Angelina Schindele, Holger Puchta
Summary: Heritable plant chromosome engineering can be achieved in somatic cells using CRISPR/Cas to induce nonhomologous double-strand break repair pathways. This technology allows for large-scale restructuring of plant chromosomes, including duplications, inversions, and translocations. The use of nonhomologous end joining pathways in somatic cells facilitates efficient chromosomal rearrangements. This breakthrough has the potential to revolutionize plant breeding.
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
Cell Biology
Maria Likhatcheva, Roben G. Gieling, James A. L. Brown, Constantinos Demonacos, Kaye J. Williams
Summary: Genotoxic stress can activate the ATM kinase, with potential involvement of Suv39H1 and Tip60 in ATM activation under hypoxic conditions.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Venturina Stagni, Alessandra Ferri, Claudia Cirotti, Daniela Barila
Summary: There is a strong interplay between autophagy and genomic stability, with recent evidence linking DNA Damage Response (DDR) and autophagy in influencing cell fate. ATM kinase plays a crucial role in balancing senescence and apoptosis in response to stimuli, and its aberrant deregulation is linked to the development of pathologies like cancer and neurodegeneration.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Immunology
Geraldine Blanchard-Rohner, Anna Peirolo, Ludivine Coulon, Christian Korff, Judit Horvath, Pierre R. Burkhard, Fabienne Gumy-Pause, Emmanuelle Ranza, Peter Jandus, Harpreet Dibra, Alexander Malcolm R. Taylor, Joel Fluss
Summary: Ataxia-telangiectasia (A-T) is a neurodegenerative and primary immunodeficiency disorder characterized by various symptoms. This study presents a case series highlighting the phenotypic variability of A-T and emphasizes the importance of early diagnosis of variant A-T and classical A-T.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Genetics & Heredity
Motohiro Yamauchi
Summary: Chromosome rearrangements are structural variations in chromosomes and are associated with a variety of human diseases. Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by chromosome rearrangements at the cellular level, particularly in T lymphocytes. The defective gene in A-T is ataxia-telangiectasia mutated (ATM), which plays a central role in cellular response to DNA damage, including suppressing chromosome rearrangements.
Article
Immunology
Ruth Pia Duecker, Lucia Gronau, Patrick C. Baer, Stefan Zielen, Ralf Schubert
Summary: Our study focused on investigating the feasibility of different approaches of hematopoietic stem cell transplantation (HSCT) for Ataxia-telangiectasia (A-T) by using Atm-deficient mice as models. The results showed that haploidentical HSCT could extend the lifespan of Atm-deficient mice and improve T-cell numbers and functionality. Interestingly, HSCT using heterozygous donor cells also led to improved survival and enhanced CD4 cell functionality in Atm-deficient mice, suggesting it as a potential strategy for A-T treatment.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Genetics & Heredity
Christina A. Gerodimos, Go Watanabe, Michael R. Lieber
Summary: The nucleosomal state imposes strict constraints on NHEJ nuclease and ligase activities, and the presence of nucleosome-wrapped DNA ends can affect the joining process.
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
Immunology
Raissa Bernardes da Silva, Willian dos Reis Bertoldo, Lucila Langoni Naves, Fernanda Bernadelli de Vito, Jeziel Dener Damasceno, Luiz Ricardo Orsini Tosi, Carlos Renato Machado, Andre Luiz Pedrosa
Summary: In this study, the DNA damage response pathways in promastigote forms of L. major were investigated. The overexpression of LmjEXO1 made the cells more susceptible to genotoxic damage, while ATR-specific inhibition made the control cells more susceptible to oxidative damage.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Junho Kim, August Yue Huang, Shelby L. Johnson, Jenny Lai, Laura Isacco, Ailsa M. Jeffries, Michael B. Miller, Michael A. Lodato, Christopher A. Walsh, Eunjung Alice Lee
Summary: This study developed a computational method, PhaseDel, to detect focal deletions and characterize underlying mechanisms in single-cell whole genome sequences (scWGS). The research found that somatic deletions increased with age and in highly expressed genes in human brain. The analysis of DNA repair-deficient diseases with progressive neurodegeneration revealed elevated somatic deletions compared to age-matched controls, suggesting a role for somatic deletions in neurodegeneration.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Changwei Chen, Jennifer R. Gallagher, Jamie Tarlton, Lidy van Aalten, Susan E. Bray, Michael L. J. Ashford, Rory J. McCrimmon, Ewan R. Pearson, Alison D. McNeilly, Calum Sutherland
Summary: Genotype may influence the therapeutic effects of metformin for type-2 diabetes, and the NPAT gene may play a role in the mechanism of metformin action.
Review
Cell Biology
Julio Aguado, Cecilia Gomez-Inclan, Hannah C. Leeson, Martin F. Lavin, Yosef Shiloh, Ernst J. Wolvetang
Summary: Ataxia-telangiectasia (A-T) is a complex disorder characterized by progressive cerebellar degeneration, immunodeficiency, radiation sensitivity, genome instability, and predisposition to cancer. The premature aging component of A-T is of great importance in driving the disease.
AGEING RESEARCH REVIEWS
(2022)
Review
Pharmacology & Pharmacy
Bhanu Priya, Srimadhavi Ravi, Sivapriya Kirubakaran
Summary: The DNA Damage and Response (DDR) pathway is crucial for maintaining genome integrity and preventing cancer development. The DDR pathway, particularly the ATM and ATR kinases, plays a vital role in recognizing and repairing DNA double-strand breaks (DSBs), a severe DNA damage that can lead to genomic instability. Cancer cells, with a high burden of DSBs, heavily rely on efficient DSB repair mechanisms for their survival. Therefore, targeting DSB repair pathways, such as ATM and ATR, can enhance the efficacy of DNA-damaging agents in cancer treatment. This review focuses on the roles of ATM and ATR in the DDR pathway, challenges in targeting these kinases, and current clinical trials of their inhibitors.
DRUG DISCOVERY TODAY
(2023)