SAMHD1 and the innate immune response to cytosolic DNA during DNA replication
Current opinion in immunology, 2019•Elsevier
Highlights•The cGAS-STING pathway signals cytosolic DNA resulting from endogenous
DNA damage.•This pathway has both pro-tumoral and anti-tumoral roles depending on the
context.•AGS genes provide new insights into the link between DNA damage and
inflammation.•The formation and rupture of micronuclei activate cGAS in the absence of
RNase H2.•SAMHD1 acts at stalled forks and prevents release of immunogenic ssDNA
fragments.Cytosolic DNA of endogenous or exogenous origin is sensed by the cGAS-STING …
DNA damage.•This pathway has both pro-tumoral and anti-tumoral roles depending on the
context.•AGS genes provide new insights into the link between DNA damage and
inflammation.•The formation and rupture of micronuclei activate cGAS in the absence of
RNase H2.•SAMHD1 acts at stalled forks and prevents release of immunogenic ssDNA
fragments.Cytosolic DNA of endogenous or exogenous origin is sensed by the cGAS-STING …
Highlights
- The cGAS-STING pathway signals cytosolic DNA resulting from endogenous DNA damage.
- This pathway has both pro-tumoral and anti-tumoral roles depending on the context.
- AGS genes provide new insights into the link between DNA damage and inflammation.
- The formation and rupture of micronuclei activate cGAS in the absence of RNase H2.
- SAMHD1 acts at stalled forks and prevents release of immunogenic ssDNA fragments.
Cytosolic DNA of endogenous or exogenous origin is sensed by the cGAS-STING pathway to activate innate immune responses. Besides microbial DNA, this pathway detects self-DNA in the cytoplasm of damaged or abnormal cells and plays a central role in antitumor immunity. The mechanism by which cytosolic DNA accumulates under genotoxic stress conditions is currently unclear, but recent studies on factors mutated in the Aicardi-Goutières syndrome cells, such as SAMHD1, RNase H2 and TREX1, are shedding new light on this key process. In particular, these studies indicate that the rupture of micronuclei and the release of ssDNA fragments during the processing of stalled replication forks and chromosome breaks represent potent inducers of the cGAS-STING pathway.
Elsevier