Functional Interfaces, Biological Pathways, and Regulations of Interferon-Related DNA Damage Resistance Signature (IRDS) Genes

Biomolecules. 2021 Apr 22;11(5):622. doi: 10.3390/biom11050622.


Interferon (IFN)-related DNA damage resistant signature (IRDS) genes are a subgroup of interferon-stimulated genes (ISGs) found upregulated in different cancer types, which promotes resistance to DNA damaging chemotherapy and radiotherapy. Along with briefly discussing IFNs and signalling in this review, we highlighted how different IRDS genes are affected by viruses. On the contrary, different strategies adopted to suppress a set of IRDS genes (STAT1, IRF7, OAS family, and BST2) to induce (chemo- and radiotherapy) sensitivity were deliberated. Significant biological pathways that comprise these genes were classified, along with their frequently associated genes (IFIT1/3, IFITM1, IRF7, ISG15, MX1/2 and OAS1/3/L). Major upstream regulators from the IRDS genes were identified, and different IFN types regulating these genes were outlined. Functional interfaces of IRDS proteins with DNA/RNA/ATP/GTP/NADP biomolecules featured a well-defined pharmacophore model for STAT1/IRF7-dsDNA and OAS1/OAS3/IFIH1-dsRNA complexes, as well as for the genes binding to GDP or NADP+. The Lys amino acid was found commonly interacting with the ATP phosphate group from OAS1/EIF2AK2/IFIH1 genes. Considering the premise that targeting IRDS genes mediated resistance offers an efficient strategy to resensitize tumour cells and enhances the outcome of anti-cancer treatment, this review can add some novel insights to the field.

Keywords: ATP; DNA; DNA damage; IRDS genes; RNA; chemotherapy and radiotherapy; functional site; interferon; protein interfaces; receptors; resistance; upstream regulator; viruses.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / physiology*
  • Cell Line, Tumor
  • DNA Damage / genetics
  • DNA Damage / physiology*
  • Drug Resistance, Neoplasm / genetics
  • Drug Resistance, Neoplasm / physiology
  • Humans
  • Interferon Regulatory Factor-7
  • Interferons / metabolism
  • Interferons / physiology*
  • Intracellular Signaling Peptides and Proteins
  • RNA, Double-Stranded
  • RNA-Binding Proteins
  • STAT1 Transcription Factor
  • Signal Transduction
  • Transcriptional Activation


  • Adaptor Proteins, Signal Transducing
  • IFIT1 protein, human
  • IFIT3 protein, human
  • IRF7 protein, human
  • Interferon Regulatory Factor-7
  • Intracellular Signaling Peptides and Proteins
  • RNA, Double-Stranded
  • RNA-Binding Proteins
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Interferons