Cadenza ad libitum: cGAS and STING showcase their versatile virtuosities in the Ca2+-dependent rescue of stalled replication forks

In this issue of Molecular Cell, Li et al. report that the cGAS-STING cytosolic dsDNA sensing pathway plays a crucial role in regulating the TRPV2 calcium channel to rescue replication forks. In this issue of Molecular Cell, Li et al. report that the cGAS-STING cytosolic dsDNA sensing pathway plays a crucial role in regulating the TRPV2 calcium channel to rescue replication forks. Cytosolic DNA sensing by cGAS/STING promotes TRPV2-mediated Ca2+ release to protect stressed replication forksLi et al.Molecular CellJanuary 24, 2023In BriefFork protection under replication stress requires [Ca2+]i elevation, but the underlying molecular mechanism is unknown. Li et al. discovered that cGAS/STING-mediated sensing of cytosolic self-DNA produced after replication stress triggers TRPV2-dependent Ca2+ release from the ER, leading to the activation of the downstream CaMKK2-AMPK-Exo1 signaling cascade for fork protection. Full-Text PDF