Wolf, Christine ; Rapp, Alexander ; Berndt, Nicole ; Staroske, Wolfgang ; Schuster, Max ; Dobrick-Mattheuer, Manuela ; Kretschmer, Stefanie ; König, Nadja ; Kurth, Thomas ; Wieczorek, Dagmar ; Kast, Karin ; Cardoso, M. Cristina ; Günther, Claudia ; Lee-Kirsch, Min Ae (2016)
RPA and Rad51 constitute a cell intrinsic mechanism to protect the cytosol from self DNA.
In: Nature communications, 7
Artikel, Bibliographie
Kurzbeschreibung (Abstract)
Immune recognition of cytosolic DNA represents a central antiviral defence mechanism. Within the host, short single-stranded DNA (ssDNA) continuously arises during the repair of DNA damage induced by endogenous and environmental genotoxic stress. Here we show that short ssDNA traverses the nuclear membrane, but is drawn into the nucleus by binding to the DNA replication and repair factors RPA and Rad51. Knockdown of RPA and Rad51 enhances cytosolic leakage of ssDNA resulting in cGAS-dependent type I IFN activation. Mutations in the exonuclease TREX1 cause type I IFN-dependent autoinflammation and autoimmunity. We demonstrate that TREX1 is anchored within the outer nuclear membrane to ensure immediate degradation of ssDNA leaking into the cytosol. In TREX1-deficient fibroblasts, accumulating ssDNA causes exhaustion of RPA and Rad51 resulting in replication stress and activation of p53 and type I IFN. Thus, the ssDNA-binding capacity of RPA and Rad51 constitutes a cell intrinsic mechanism to protect the cytosol from self DNA.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2016 |
| Autor(en): | Wolf, Christine ; Rapp, Alexander ; Berndt, Nicole ; Staroske, Wolfgang ; Schuster, Max ; Dobrick-Mattheuer, Manuela ; Kretschmer, Stefanie ; König, Nadja ; Kurth, Thomas ; Wieczorek, Dagmar ; Kast, Karin ; Cardoso, M. Cristina ; Günther, Claudia ; Lee-Kirsch, Min Ae |
| Art des Eintrags: | Bibliographie |
| Titel: | RPA and Rad51 constitute a cell intrinsic mechanism to protect the cytosol from self DNA. |
| Sprache: | Englisch |
| Publikationsjahr: | 2016 |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Nature communications |
| Jahrgang/Volume einer Zeitschrift: | 7 |
| Kurzbeschreibung (Abstract): | Immune recognition of cytosolic DNA represents a central antiviral defence mechanism. Within the host, short single-stranded DNA (ssDNA) continuously arises during the repair of DNA damage induced by endogenous and environmental genotoxic stress. Here we show that short ssDNA traverses the nuclear membrane, but is drawn into the nucleus by binding to the DNA replication and repair factors RPA and Rad51. Knockdown of RPA and Rad51 enhances cytosolic leakage of ssDNA resulting in cGAS-dependent type I IFN activation. Mutations in the exonuclease TREX1 cause type I IFN-dependent autoinflammation and autoimmunity. We demonstrate that TREX1 is anchored within the outer nuclear membrane to ensure immediate degradation of ssDNA leaking into the cytosol. In TREX1-deficient fibroblasts, accumulating ssDNA causes exhaustion of RPA and Rad51 resulting in replication stress and activation of p53 and type I IFN. Thus, the ssDNA-binding capacity of RPA and Rad51 constitutes a cell intrinsic mechanism to protect the cytosol from self DNA. |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Cell Biology and Epigenetics |
| Hinterlegungsdatum: | 31 Mai 2016 06:48 |
| Letzte Änderung: | 31 Mai 2016 06:48 |
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