Work

Faculty Opinions recommendation of Mitotic progression following DNA damage enables pattern recognition within micronuclei.

Year: 2019

Type: peer-review

Abstract: Inflammatory gene expression following genotoxic cancer therapy is well documented, yet the events underlying its induction remain poorly understood.Inflammatory cytokines modify the tumor microenvironment by recruiting immune cells and are critical for both local and systemic (abscopal) tumor responses to radiotherapy 1 .An enigmatic feature of this phenomenon is its delayed onset (days), in contrast to the acute DNA damage responses that occur in minutes to hours.Such dichotomous kinetics implicate additional rate limiting steps that are essential for DNA-damage induced inflammation.Here, we show that cell cycle progression through mitosis following DNA double-strand breaks (DSBs) leads to the formation of micronuclei, which precede activation of inflammatory signaling and are a repository for the pattern recognition receptor cGAS.Inhibiting progression through mitosis or loss of pattern recognition by cGAS-STING impaired interferon signaling.Moreover, STING loss prevented the regression of abscopal tumors in the context of ionizing radiation and immune checkpoint blockade in vivo.These findings Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.

Source: Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature

DOI: 10.3410/f.727856929.793558741

Author: Jan Karlseder

Institution: Salk Institute for Biological Studies

Language: English

Topic: interferon and immune responses

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Institutes of Health