Mechanistic link between DNA damage sensing, repairing and signaling factors and immune signaling

Shibani Mukherjee, Salim Abdisalaam, Souparno Bhattacharya, Kalayarasan Srinivasan, Debapriya Sinha, Aroumougame Asaithamby

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Scopus citations

Abstract

Previously, DNA damage sensing, repairing and signaling machineries were thought to mainly suppress genomic instability in response to genotoxic stress. Emerging evidence indicates a crosstalk between DNA repair machinery and the immune system. In this chapter, we attempt to decipher the molecular choreography of how factors, including ATM, BRCA1, DNA-PK, FANCA/D2, MRE11, MUS81, NBS1, RAD51 and TREX1, of multiple DNA metabolic processes are directly or indirectly involved in suppressing cytosolic DNA sensing pathway-mediated immune signaling. We provide systematic details showing how different DDR factors’ roles in modulating immune signaling are not direct, but are rather a consequence of their inherent ability to sense, repair and signal in response to DNA damage. Unexpectedly, most DDR factors negatively impact the immune system; that is, the immune system shows defective signaling if there are defects in DNA repair pathways. Thus, in addition to their known DNA repair and replication functions, DDR factors help prevent erroneous activation of immune signaling. A more precise understanding of the mechanisms by which different DDR factors function in immune signaling can be exploited to redirect the immune system for both preventing and treating autoimmunity, cellular senescence and cancer in humans.

Original languageEnglish (US)
Title of host publicationAdvances in Protein Chemistry and Structural Biology
PublisherAcademic Press Inc.
Pages297-324
Number of pages28
DOIs
StatePublished - Jan 1 2019

Publication series

NameAdvances in Protein Chemistry and Structural Biology
Volume115
ISSN (Print)1876-1623

Keywords

  • cGAS
  • DDR
  • Genomic instability
  • Innate immunity
  • Micronuclei
  • MRE11
  • NBS1
  • RAD51
  • Senescence
  • STING

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry

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  • Cite this

    Mukherjee, S., Abdisalaam, S., Bhattacharya, S., Srinivasan, K., Sinha, D., & Asaithamby, A. (2019). Mechanistic link between DNA damage sensing, repairing and signaling factors and immune signaling. In Advances in Protein Chemistry and Structural Biology (pp. 297-324). (Advances in Protein Chemistry and Structural Biology; Vol. 115). Academic Press Inc.. https://doi.org/10.1016/bs.apcsb.2018.11.004