MRE11-dependent instability in mitochondrial DNA fork protection activates a cGAS immune signaling pathway.
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ABSTRACT:
SUBMITTER: Luzwick JW
PROVIDER: S-EPMC8673762 | biostudies-literature | 2021 Dec
REPOSITORIES: biostudies-literature
Publications
MRE11-dependent instability in mitochondrial DNA fork protection activates a cGAS immune signaling pathway.
Luzwick Jessica W JW Dombi Eszter E Boisvert Rebecca A RA Roy Sunetra S Park Soyoung S Kunnimalaiyaan Selvi S Goffart Steffi S Schindler Detlev D Schlacher Katharina K
Science advances 20211215 51
Mitochondrial DNA (mtDNA) instability activates cGAS-dependent innate immune signaling by unknown mechanisms. Here, we find that Fanconi anemia suppressor genes are acting in the mitochondria to protect mtDNA replication forks from instability. Specifically, Fanconi anemia patient cells show a loss of nascent mtDNA through MRE11 nuclease degradation. In contrast to DNA replication fork stability, which requires pathway activation by FANCD2-FANCI monoubiquitination and upstream FANC core complex ...[more]
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