Mechanisms of Immune Sensing of DNA Damage

Anna M Goddard; Min-Guk Cho; Lynn M Lerner; Gaorav P Gupta

doi:10.1016/j.jmb.2023.168424

Mechanisms of Immune Sensing of DNA Damage

J Mol Biol. 2024 Feb 15;436(4):168424. doi: 10.1016/j.jmb.2023.168424. Epub 2023 Dec 29.

Authors

Anna M Goddard¹, Min-Guk Cho², Lynn M Lerner³, Gaorav P Gupta⁴

Affiliations

¹ Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: annago4@email.unc.edu.
² Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
³ Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Genetics and Molecular Biology Curriculum, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁴ Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

PMID: 38159716
DOI: 10.1016/j.jmb.2023.168424

Abstract

Genomic stability relies on a multifaceted and evolutionarily conserved DNA damage response (DDR). In multicellular organisms, an integral facet of the DDR involves the activation of the immune system to eliminate cells with persistent DNA damage. Recent research has shed light on a complex array of nucleic acid sensors crucial for innate immune activation in response to oncogenic stress-associated DNA damage, a process vital for suppressing tumor formation. Yet, these immune sensing pathways may also be co-opted to foster tolerance of chromosomal instability, thereby driving cancer progression. This review aims to provide an updated overview of how the innate immune system detects and responds to DNA damage. An improved understanding of the regulatory intricacies governing this immune response may uncover new avenues for cancer prevention and therapeutic intervention.

Keywords: DNA Damage; RNA sensing; cytosolic DNA sensing; immune sensing; sensors of replication-associated DNA damage.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

DNA Damage* / immunology
DNA Repair
Humans
Innate Immunity Recognition*
Neoplasms* / genetics
Neoplasms* / immunology
Neoplasms* / pathology