DNA-protein cross-links promote cGAS-STING-driven premature aging and embryonic lethality.

Ines Tomaskovic, Cristian Prieto-Garcia, Maria Boskovic, Mateo Glumac, Tsung-Lin Tsai, Thorsten Mosler, Rubina Kazi, Rajeshwari Rathore, Jorge Andrade, Marina Hoffmann, Giulio Giuliani, Anne-Claire Jacomin, Raquel S Pereira, Elias Knop, Laurens Wachsmuth, Petra Beli, Koraljka Husnjak, Manolis Pasparakis, Andrea Ablasser, Daniela S Krause, Michael Potente, Stamatis Papathanasiou, Janos Terzic, Ivan Dikic

Institute of Biochemistry II, Faculty of Medicine, Goethe University Frankfurt, Frankfurt, Germany.Institute of Biochemistry II, Faculty of Medicine, Goethe University Frankfurt, Frankfurt, Germany. · pubmed

Paper

Abstract

DNA-protein cross-links (DPCs) are highly toxic DNA lesions that block replication and transcription, but their impact on organismal physiology is unclear. We identified a role for the metalloprotease SPRTN in preventing DPC-driven immunity and its pathological consequences. Loss of SPRTN activity during replication and mitosis lead to unresolved DNA damage, chromosome segregation errors, micronuclei formation, and cytosolic DNA release that activates the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. In a

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Research summary

The paper claims that loss of SPRTN activity leads to DNA damage that activates the cGAS-STING pathway, contributing to premature aging. This research addresses the mechanisms of DNA damage and its implications for aging, which are central to understanding the root causes of aging and age-related diseases.

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