When DNA-damage responses meet innate and adaptive immunity.

Area of Science:

• Molecular Biology
• Immunology
• Genetics

Background:

• Cellular proliferation and various insults can cause DNA damage, necessitating complex DNA-Damage Response (DDR) networks in multicellular organisms.
• Multiple repair pathways, including Base-Excision Repair (BER), Nucleotide Excision Repair (NER), and Homologous Recombination (HR), exist to address different types of DNA damage.
• Both innate and adaptive immune responses are crucial for maintaining homeostasis against mutations and pathogens.

Purpose of the Study:

• To review recent advancements in the interplay between DDR components and immunological responses.
• To highlight the dual roles of DDR network's immune modulators.
• To explore potential therapeutic applications stemming from this interaction.

Main Methods:

• Literature review of recent scientific developments.
• Analysis of signaling pathways connecting DDR and immune responses, such as the cGAS-STING pathway.
• Examination of the functional roles of DDR components in immune modulation.

Main Results:

• New research reveals a close relationship between DDR components and the immune system.
• Immune effectors like the cyclic GMP-AMP synthase (cGAS)-Stimulator of Interferon Genes (STING) pathway link DDR and immune responses.
• DDR components can act as sensors for DNA damage-induced immune responses and modulate inflammatory cytokine generation or programmed cell death.

Conclusions:

• Defects in DDR compromise genomic stability and immune function, potentially leading to cancer and autoimmune diseases.
• The dual functions of DDR network's immune modulators provide novel insights.
• This understanding may pave the way for new treatments for DNA damage-related infectious diseases and cancer, including targeted immunotherapies.