Rad50

Rad50 is a protein involved in DNA repair and maintenance, primarily functioning as part of the MRE11-RAD50-NBS1 (MRN) complex. This complex plays a crucial role in the cellular response to double-strand breaks (DSBs), a type of DNA damage that can be highly detrimental if not repaired properly. Rad50 is essential for the recruitment of repair proteins to the site of damage and for the processing of DNA ends, which is a critical step in non-homologous end joining (NHEJ) and homologous recombination (HR) pathways.

The Rad50 protein contains a conserved ATPase domain that contributes to its function in DNA repair. It also possesses a coiled-coil domain that facilitates protein-protein interactions, helping to assemble the MRN complex. Rad50’s structure includes a central rod-like domain that interacts with MRE11 and NBS1, forming a stable tripartite complex. This complex is particularly important in the early stages of DSB repair, including the resection of DNA ends and the stabilization of broken DNA strands.

Mutations in the RAD50 gene can lead to severe genetic disorders, such as ataxia telangiectasia-like disorder (ATLD) and Nijmegen breakage syndrome (NBS). Individuals with these conditions often exhibit increased sensitivity to ionizing radiation, chromosomal instability, and developmental abnormalities. Rad50’s role in maintaining genomic integrity highlights its importance in preventing cancer and ensuring proper cellular function.

Research into Rad50 has expanded our understanding of DNA repair mechanisms and the potential for therapeutic interventions in diseases associated with defective DNA repair pathways. Ongoing studies continue to explore its interactions with other proteins and its contributions to cellular stress responses.