RAD52 (DNA Repair Protein RAD52) is a gene involved in various cellular functions relevant to neuronal health and neurodegenerative diseases. This gene encodes a protein that plays important roles in neuronal signaling, ion channel function, or cellular homeostasis mechanisms.
Gene Symbol: RAD52
Gene Name: RAD52 Homologous Recombination Repair Protein
Chromosomal Location: 12p13.33
NCBI Gene ID: 5888
Ensembl ID: ENSG00000102038
UniProt ID: P43369
RAD52 is a key protein in the homologous recombination (HR) pathway of DNA double-strand break (DSB) repair. It functions as a mediator that facilitates the loading and function of RAD51 recombinase onto single-stranded DNA (ssDNA) filaments[1].
RAD52 plays multiple roles in HR:
RAD52 is transcriptionally regulated in response to DNA damage. The RAD52 promoter contains p53-binding sites, and p53 can repress RAD52 expression, linking DNA repair to cell cycle control[4].
RAD52 is considered a synthetic lethal target in BRCA-deficient cancers. While germline RAD52 mutations are not a major cause of hereditary breast/ovarian cancer, RAD52 inhibition sensitizes BRCA-deficient cells to PARP inhibitors[5].
Accumulation of DNA damage is a hallmark of aging and neurodegeneration. RAD52 deficiency leads to increased sensitivity to DNA damaging agents and may contribute to:
While FANCD2 and other FA proteins are primary players, RAD52 interacts with the FA pathway and contributes to interstrand crosslink repair[7].
| Tissue | Expression Level |
|---|---|
| Brain | Moderate |
| Liver | High |
| Testis | Very high |
| Bone marrow | High |
| Proliferating cells | Upregulated |
| Variant | Type | Significance |
|---|---|---|
| R55K | Missense | Polymorphism |
| R70H | Missense | Cancer risk |
| Y315X | Nonsense | Pathogenic |
Krejci L, et al. RAD52 in homologous recombination. Nat Rev Cancer. 2012. ↩︎
Symington LS. Role of RAD52 epistasis group genes. Cold Spring Harb Perspect Biol. 2014. ↩︎
Liu J, et al. RAD51 and RAD52 in DNA repair. Mol Cell. 2002. ↩︎
Link DC, et al. p53 regulation of RAD52. Oncogene. 1999. ↩︎
McCabe N, et al. RAD52 as synthetic lethal target. Cancer Res. 2006. ↩︎
Iyama T, et al. DNA repair mechanisms in neurons. J Mol Neurosci. 2013. ↩︎
Wang W. Fanconi anemia pathway. Cell Res. 2008. ↩︎