Moonlighting chromatin: when DNA escapes nuclear control

Singh J, Boettcher M, Dölling M, Heuer A, Hohberger B, Leppkes M, Naschberger E, Schapher M, Schauer C, Schoen J, Stürzl M, Vitkov L, Wang H, Zlatar L, Schett G, Pisetsky DS, Liu ML, Herrmann M, Knopf J (2023)

Publication Type: Journal article, Review article

Publication year: 2023

Journal

Cell Death and Differentiation Nature Publishing Group: Open Access Hybrid Model Option B

DOI: 10.1038/s41418-023-01124-1

Abstract

Extracellular chromatin, for example in the form of neutrophil extracellular traps (NETs), is an important element that propels the pathological progression of a plethora of diseases. DNA drives the interferon system, serves as autoantigen, and forms the extracellular scaffold for proteins of the innate immune system. An insufficient clearance of extruded chromatin after the release of DNA from the nucleus into the extracellular milieu can perform a secret task of moonlighting in immune-inflammatory and occlusive disorders. Here, we discuss (I) the cellular events involved in the extracellular release of chromatin and NET formation, (II) the devastating consequence of a dysregulated NET formation, and (III) the imbalance between NET formation and clearance. We include the role of NET formation in the occlusion of vessels and ducts, in lung disease, in autoimmune diseases, in chronic oral disorders, in cancer, in the formation of adhesions, and in traumatic spinal cord injury. To develop effective therapies, it is of utmost importance to target pathways that cause decondensation of chromatin during exaggerated NET formation and aggregation. Alternatively, therapies that support the clearance of extracellular chromatin are conceivable. [Figure not available: see fulltext.].

Authors with CRIS profile

Jeeshan Singh Department of Medicine 3 – Rheumatology and Immunology Bettina Hohberger Department of Ophthalmology Moritz Leppkes Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Elisabeth Naschberger Department of Surgery Mirco Schapher Department of Otorhinolaryngology – Head and Neck Surgery (HNO-Klinik) Christine Schauer Department of Medicine 3 – Rheumatology and Immunology Janina Schoen Department of Medicine 3 – Rheumatology and Immunology Michael Stürzl Professur für Molekulare und Experimentelle Chirurgie Han Wang Medizinische Fakultät Leticija Zlatar Department of Medicine 3 – Rheumatology and Immunology Georg Schett Lehrstuhl für Innere Medizin III Martin Herrmann Department of Medicine 3 – Rheumatology and Immunology Jasmin Knopf Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

Universitätsklinikum Magdeburg A.ö.R. DE Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE) Universitätsklinikum des Saarlandes (UKS) DE Germany (DE) Penn Medicine US United States (USA) (US) Duke University Medical Center US United States (USA) (US) Universitätsklinikum Mannheim DE Germany (DE)

How to cite

APA:

Singh, J., Boettcher, M., Dölling, M., Heuer, A., Hohberger, B., Leppkes, M.,... Knopf, J. (2023). Moonlighting chromatin: when DNA escapes nuclear control. Cell Death and Differentiation. https://doi.org/10.1038/s41418-023-01124-1

MLA:

Singh, Jeeshan, et al. "Moonlighting chromatin: when DNA escapes nuclear control." Cell Death and Differentiation (2023).

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