Calcitriol Prevents RAD51 Loss and cGAS-STING-IFN Response Triggered by Progerin.

ABSTRACT: Hutchinson Gilford progeria syndrome (HGPS) is a devastating accelerated aging disease caused by LMNA gene mutation. The truncated lamin A protein produced "progerin" has a dominant toxic effect in cells, causing disruption of nuclear architecture and chromatin structure, genomic instability, gene expression changes, oxidative stress, and premature senescence. It was previously shown that progerin-induced genomic instability involves replication stress (RS), characterized by replication fork stalling and nuclease-mediated degradation of stalled forks. RS is accompanied by activation of cGAS/STING cytosolic DNA sensing pathway and STAT1-regulated interferon (IFN)-like response. It is also found that calcitriol, the active hormonal form of vitamin D, rescues RS and represses the cGAS/STING/I

SUBMITTER: Coll-Bonfill N 

PROVIDER: S-EPMC7117971 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature