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

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

Research output: Contribution to journalArticle

1 Citation (Scopus)

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)
JournalAdvances in Protein Chemistry and Structural Biology
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Immunologic Factors
DNA Damage
Immune System
DNA Repair
Immune system
DNA
Repair
Genomic Instability
Cell Aging
DNA Replication
Autoimmunity
Automatic teller machines
Crosstalk
Machinery
Neoplasms
Chemical activation
Defects

Keywords

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

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry

Cite this

Mechanistic link between DNA damage sensing, repairing and signaling factors and immune signaling. / Mukherjee, Shibani; Abdisalaam, Salim; Bhattacharya, Souparno; Srinivasan, Kalayarasan; Sinha, Debapriya; Aroumougame, Asaithamby.

In: Advances in Protein Chemistry and Structural Biology, 01.01.2019.

Research output: Contribution to journalArticle

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