Format

Send to

Choose Destination
Nucleic Acids Res. 2017 May 5;45(8):4590-4605. doi: 10.1093/nar/gkx126.

RAD51 interconnects between DNA replication, DNA repair and immunity.

Author information

1
Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
2
Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
3
Department of Molecular Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Abstract

RAD51, a multifunctional protein, plays a central role in DNA replication and homologous recombination repair, and is known to be involved in cancer development. We identified a novel role for RAD51 in innate immune response signaling. Defects in RAD51 lead to the accumulation of self-DNA in the cytoplasm, triggering a STING-mediated innate immune response after replication stress and DNA damage. In the absence of RAD51, the unprotected newly replicated genome is degraded by the exonuclease activity of MRE11, and the fragmented nascent DNA accumulates in the cytosol, initiating an innate immune response. Our data suggest that in addition to playing roles in homologous recombination-mediated DNA double-strand break repair and replication fork processing, RAD51 is also implicated in the suppression of innate immunity. Thus, our study reveals a previously uncharacterized role of RAD51 in initiating immune signaling, placing it at the hub of new interconnections between DNA replication, DNA repair, and immunity.

PMID:
28334891
PMCID:
PMC5416901
DOI:
10.1093/nar/gkx126
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center