RAD51 interconnects between DNA replication, DNA repair and immunity

Souparno Bhattacharya, Kalayarasan Srinivasan, Salim Abdisalaam, Fengtao Su, Prithvi Raj, Igor Dozmorov, Ritu Mishra, Edward K. Wakeland, Subroto Ghose, Shibani Mukherjee, Aroumougame Asaithamby

Research output: Contribution to journalArticle

39 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4590-4605
Number of pages16
JournalNucleic Acids Research
Volume45
Issue number8
DOIs
StatePublished - 2017

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ASJC Scopus subject areas

  • Genetics

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