Related Experiment Video
Updated: Dec 28, 2025

Techniques to Induce and Quantify Cellular Senescence
Published on: May 1, 2017
Topoisomerase 1 cleavage complex enables pattern recognition and inflammation during senescence
Bo Zhao1, Pingyu Liu1, Takeshi Fukumoto1
1Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, PA, 19104, USA.
Abstract:
Cyclic cGMP-AMP synthase (cGAS) is a pattern recognition cytosolic DNA sensor that is essential for cellular senescence. cGAS promotes inflammatory senescence-associated secretory phenotype (SASP) through recognizing cytoplasmic chromatin during senescence. cGAS-mediated inflammation is essential for the antitumor effects of immune checkpoint blockade. However, the mechanism by which cGAS recognizes cytoplasmic chromatin is unknown. Here we show that topoisomerase 1-DNA covalent cleavage complex (TOP1cc) is both necessary and sufficient for cGAS-mediated cytoplasmic chromatin recognition and SASP during senescence. TOP1cc localizes to cytoplasmic chromatin and TOP1 interacts with cGAS to enhance the binding of cGAS to DNA. Retention of TOP1cc to cytoplasmic chromatin depends on its stabilization by the chromatin architecture protein HMGB2. Functionally, the HMGB2-TOP1cc-cGAS axis determines the response of orthotopically transplanted ex vivo therapy-induced senescent cells to immune checkpoint blockade in vivo. Together, these findings establish a HMGB2-TOP1cc-cGAS axis that enables cytoplasmic chromatin recognition and response to immune checkpoint blockade.
More Related Videos
08:56Simultaneous Imaging and Flow-Cytometry-based Detection of Multiple Fluorescent Senescence Markers in Therapy-Induced Senescent Cancer Cells
Published on: July 12, 2022
13:59A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence
Published on: August 12, 2018
Related Concept Videos
Caspases
DNA Topoisomerases
Types and Mechanism of action
Topoisomerases are divided into two main types. ...
Replicative Cell Senescence
Anaphase Promoting Complex
Restarting Stalled Replication Forks
The Intrinsic Apoptotic Pathway