Article
Dermatology
Nicole Berndt, Christine Wolf, Kristina Fischer, Emanuel Cura Costa, Peter Knuschke, Nick Zimmermann, Franziska Schmidt, Martin Merkel, Osvaldo Chara, Min Ae Lee-Kirsch, Claudia Gunther
Summary: The exonuclease TREX1 plays a protective role in preventing DNA accumulation and innate immune activation. TREX1 mutations lead to chronic DNA damage, IFN-1 response, and associated diseases such as Aicardi-Goutières syndrome, familial chilblain lupus, and systemic lupus erythematosus. Patients with lupus and TREX1 mutation show enhanced photosensitivity and increased levels of DNA damage in response to UV radiation, which can trigger disease flares.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Kuan-Wei Huang, Chia-Yun Wu, Shu-Ing Toh, Tung-Chang Liu, Chun- Tu, Yin-Hsin Lin, An-Ju Cheng, Ya-Ting Kao, Jhih-Wei Chu, Yu-Yuan Hsiao
Summary: Dysfunctional TREX1 leads to accumulation of endogenous DNA and RNA, triggering immune response. TREX1 can digest RNA and DNA/RNA hybrids, but RNA conformation rigidity reduces its exonuclease activity.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Monisankar Ghosh, Suchandrima Saha, Jinyu Li, David C. Montrose, Luis A. Martinez
Summary: Tumor suppression by TP53 involves both cell-autonomous and non-cell-autonomous mechanisms. This study reveals that p53 promotes the degradation of TREX1, leading to cytosolic dsDNA accumulation and activation of the cGAS/STING pathway, resulting in induction of type I interferons. The activation of the cGAS/STING pathway is crucial for p53's tumor suppressor activities.
Review
Dermatology
Claudia Guenther, Joerg Wenzel
Summary: Cutaneous lupus erythematosus has a broad clinical spectrum and can either involve or not involve the systemic. The disease is characterized by a loss of tolerance to endogenous antigens and a chronic relapsing activation of the immune system. Research has expanded our understanding of the disease, but treatment options remain limited.
JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT
(2023)
Article
Biochemistry & Molecular Biology
Suresh Pal, Bryce Plapp
Summary: X-ray crystallography has revealed that the threonine residue (Thr-45) in the yeast alcohol dehydrogenase (ADH1) plays an important role in catalysis and its substitution results in a significant decrease in catalytic efficiency. Conformational changes of the enzyme and ligand exchanges on the catalytic zinc are severely impacted by the removal of the hydroxyethyl group of Thr-45.
CHEMICO-BIOLOGICAL INTERACTIONS
(2021)
Article
Biochemistry & Molecular Biology
Roy Anindya
Summary: The presence of DNA in the cytoplasm of tumor cells can induce the production of type-I IFNs by dendritic cells, but it can also lead to senescence and immune surveillance in tumor cells. However, various factors can cause the persistent accumulation of DNA in the cytoplasm of tumor cells, resulting in aberrant activation of the type I IFN pathway and chronic inflammation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2022)
Review
Dermatology
Claudia Guenther, Joerg Wenzel
Summary: Cutaneous lupus erythematosus can present with or without systemic involvement, resulting in a wide range of clinical manifestations. The disease is characterized by a loss of tolerance to endogenous antigens and chronic activation of the immune system. Although our understanding of the disease pathogenesis has improved, treatment options remain limited. Biologics targeting BLyS or the type I interferon receptor have shown promising results in patients with cutaneous involvement and systemic lupus erythematosus. However, conducting clinical trials is challenging due to the variability of symptoms. Nonetheless, focusing on cutaneous manifestations as primary endpoints may lead to better treatment options for SLE in the future.
JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT
(2023)
Article
Biochemistry & Molecular Biology
Guilherme Pedreira de Freitas Nader, Sonia Aguera-Gonzalez, Fiona Routet, Matthieu Gratia, Mathieu Maurin, Valeria Cancila, Clotilde Cadart, Andrea Palamidessi, Rodrigo Nalio Ramos, Mabel San Roman, Matteo Gentili, Ayako Yamada, Alice Williart, Catalina Lodillinsky, Emilie Lagoutte, Catherine Villard, Jean-Louis Viovy, Claudio Tripodo, Jerome Galon, Giorgio Scita, Nicolas Manel, Philippe Chavrier, Matthieu Piel
Summary: Nuclear envelope ruptures induced DNA damage in non-transformed cells promoting senescence and in human breast cancer cells inducing an invasive phenotype. The ER-associated exonuclease TREX1 translocated into the nucleus after rupture and was necessary for DNA damage induction. This study suggests that DNA damage in mechanically challenged nuclei may affect tissue pathophysiology by modulating proliferation and extracellular matrix degradation.
Article
Biochemistry & Molecular Biology
Avigail Stokar-Avihail, Taya Fedorenko, Jens Hor, Jeremy Garb, Azita Leavitt, Adi Millman, Gabriela Shulman, Nicole Wojtania, Sarah Melamed, Gil Amitai, Rotem Sorek
Summary: In recent years, various defense systems against phages have been found in bacteria. However, the mechanism of how these systems sense phage infection remains unknown. To address this question, the researchers isolated 177 phage mutants that can evade 15 different defense systems. These mutants were found to have mutations in the gene sensed by the defense system, providing insights into the determinants of phage sensitivity. The study identifies specific determinants of different retron systems and reveals phage-encoded triggers for abortive infection systems, shedding light on how bacterial immune systems sense phage invaders.
Article
Biochemistry & Molecular Biology
Wen Zhou, Lisa Mohr, John Maciejowski, Philip J. Kranzusch
Summary: The phase separation of cGAS-DNA is critical for efficient sensing of immunostimulatory DNA, as it limits the activity of the cytosolic exonuclease TREX1. This selective environment suppresses TREX1 function and restricts DNA degradation, balancing cytosolic DNA degradation and innate immune activation.
Review
Urology & Nephrology
Sladjana Skopelja-Gardner, Jie An, Keith B. Elkon
Summary: Cells have sensors that recognize nucleic acids, triggering immune responses and promoting antiviral states. The cGAS-STING pathway, a recently identified DNA sensor pathway, binds DNA and produces a messenger molecule called cGAMP, leading to an inflammatory response. This pathway is involved in various diseases and has therapeutic potential.
NATURE REVIEWS NEPHROLOGY
(2022)
Review
Immunology
Meiying Wang, Snehin Rajkumar, Yupeng Lai, Xingjiao Liu, Jing He, Tatsuya Ishikawa, Dhiraj Nallapothula, Ram Raj Singh
Summary: This article describes the potential role of tertiary lymphoid structures (TLS) in the pathogenesis of autoimmune diseases, focusing on lupus nephritis. The presence of TLS in the kidneys is associated with severe inflammation, higher disease activity, and poor response to treatment. TLS may contribute to the development of lupus nephritis by increasing local immune response and supporting the production of autoantibodies. However, the mechanisms underlying TLS formation and their exact role in lupus nephritis are not fully understood.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Naeun Yoon, Ah-Kyung Jang, Yerim Seo, Byung Hwa Jung
Summary: This paper outlines recent advances in metabolomics research of autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus, describing newly discovered biomarkers and metabolic mechanism studies for these diseases. It also presents studies elucidating the metabolic mechanisms underlying these diseases and summarizes biomarker studies aimed at predicting personalized medicine and drug response.
Article
Immunology
Yan Wang, Zunyun Fu, Xutong Li, Yinming Liang, Siyu Pei, Shumeng Hao, Qingchen Zhu, Tao Yu, Yifei Pei, Jia Yuan, Jialin Ye, Jiemeng Fu, Jing Xu, Jin Hong, Ruirui Yang, Hui Hou, Xinfang Huang, Chao Peng, Mingyue Zheng, Yichuan Xiao
Summary: The study reveals that the KU complex is abundantly expressed in CD4(+) T cells and enhances cell activation and proliferation in aged mice with EAE pathology by facilitating DNA-PKcs recruitment and phosphorylation of the kinase ZAK. A specific ZAK inhibitor can alleviate EAE pathology in aged mice.
Article
Virology
Benem-Orom Davids, Muthukumar Balasubramaniam, Nicklas Sapp, Prem Prakash, Shalonda Ingram, Min Li, Robert Craigie, Thomas Hollis, Jui Pandhare, Chandravanu Dash
Summary: HIV-1 infection is associated with upregulation, perinuclear accumulation, and nuclear localization of TREX1. TREX1 plays a role in promoting HIV-1 integration by enhancing PIC activity and preferentially degrading viral DNAs that are incompatible with chromosomal insertion.
JOURNAL OF VIROLOGY
(2021)
Article
Genetics & Heredity
Marit A. E. van Bueren, Aniek Janssen
Summary: Eukaryotic nuclei rely on multiple repair pathways to accurately repair DNA damage, particularly in chromatin domains enriched for repetitive DNA sequences. Tailored repair mechanisms are necessary to maintain genome stability in these domains.