RAD50 Gene

RAD50 also called "RAD50 Double Strand Break Repair Protein" is a protein coding gene located on chromosome 5q31.1. The protein of the same name encoded by this gene bears a strong resemblance to Saccharomyces cerevisiae Rad50, a protein involved in the repair of DNA double strand breaks.

The RAD50 protein, together with MRE11 and NBS1, forms a protein complex(MRE11-RAD50-NBS1 complex) that binds to DNA and performs numerous enzymatic activities required for the non-homologous joining of DNA ends. The MRE11-RAD50-NBS1 complex plays a critical role in DNA damage recognition and repair. The complex possesses a single-stranded endonuclease activity and a double-stranded 3'-5' exonuclease activity provided by MRE11. RAD50 may be required to bind DNA ends and keep them in close proximity.

Mutations in any member of this complex may lead to hypersensitivity to genotoxic agents and predisposition to malignancy. MRN can interfere with cancer therapy and is an attractive target for precision medicine.

Single nucleotide polymorphisms in the human Th2 cytokine locus, particularly in a locus control region within the DNA repair gene RAD50 that contains multiple RAD50-DNase1 hypersensitive sites (RHS), have been clearly associated with atopic traits in genome-wide association studies (GWAS).

Human RHS7 contributes critically to the regulation of gene transcription. The common atopy-associated polymorphism rs2240032 affects transcriptional activity and transcription factor binding (Kretschmer A et al. 2014).

Mutations in this gene may be associated with the very rare Nijmegen breakage syndrome . Related pathways include cell cycle, mitosis, and Integrated Breast Cancer Pathway. Gene Ontology (GO) annotations for this gene include ATPase activity and ATP-dependent DNA helicase activity.