RAD50

RAD50

RAD50 is a gene that encodes a protein involved in the repair of DNA double-strand breaks. It is a crucial component of the MRN complex, which also includes MRE11 and NBS1. This complex plays a significant role in the maintenance of genomic stability, DNA repair, and the activation of the DNA damage response.

Function

The RAD50 protein is a part of the MRN complex, which is essential for the detection and repair of DNA double-strand breaks. RAD50 possesses ATPase activity and is involved in the tethering of DNA ends, facilitating their repair. The MRN complex acts as a sensor for DNA damage and is involved in the activation of ATM kinase, which phosphorylates several key proteins involved in the DNA damage response.

Structure

RAD50 is characterized by its coiled-coil domains and a zinc-hook motif, which are critical for its function in DNA repair. The zinc-hook motif allows RAD50 to form a homodimer, which is essential for the bridging of DNA ends. The ATPase domain of RAD50 is involved in the regulation of the complex's activity and its interaction with DNA.

Role in DNA Repair

RAD50, as part of the MRN complex, is involved in several DNA repair pathways, including homologous recombination and non-homologous end joining. It is particularly important in the early steps of homologous recombination, where it helps to process DNA ends to facilitate strand invasion and exchange.

Clinical Significance

Mutations in the RAD50 gene can lead to genomic instability and are associated with several human diseases, including Nijmegen breakage syndrome and Ataxia-telangiectasia-like disorder. These conditions are characterized by increased sensitivity to DNA-damaging agents, cancer predisposition, and immunodeficiency.

Research and Therapeutic Implications

Understanding the function of RAD50 and the MRN complex is crucial for developing therapeutic strategies for diseases associated with DNA repair defects. Targeting the MRN complex has potential implications in cancer therapy, particularly in enhancing the efficacy of radiation therapy and chemotherapy by exploiting the DNA repair deficiencies in cancer cells.

Also see

• MRN complex
• MRE11
• NBS1
• DNA repair
• Homologous recombination
• Non-homologous end joining
• ATM kinase