TY - JOUR
T1 - RAD51 interconnects between DNA replication, DNA repair and immunity
AU - Bhattacharya, Souparno
AU - Srinivasan, Kalayarasan
AU - Abdisalaam, Salim
AU - Su, Fengtao
AU - Raj, Prithvi
AU - Dozmorov, Igor
AU - Mishra, Ritu
AU - Wakeland, Edward K.
AU - Ghose, Subroto
AU - Mukherjee, Shibani
AU - Asaithamby, Aroumougame
N1 - Funding Information:
National Aeronautics and Space Administration [NNX13AD57G and NNX15AE06G]; Cancer Prevention and Research Institute of Texas [RP160520]; National Institute of Health [R01AG053341] to A.A. Funding for open access charge: National Aeronautics and Space Administration.
Publisher Copyright:
© The Author(s) 2017.
PY - 2017/5/5
Y1 - 2017/5/5
N2 - 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.
AB - 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.
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U2 - 10.1093/nar/gkx126
DO - 10.1093/nar/gkx126
M3 - Article
C2 - 28334891
AN - SCOPUS:85020236679
SN - 0305-1048
VL - 45
SP - 4590
EP - 4605
JO - Nucleic acids research
JF - Nucleic acids research
IS - 8
ER -