RAD52

RAD52

RAD52 is a protein that plays a crucial role in the DNA repair process, specifically in the homologous recombination (HR) pathway. It is a key component in the repair of double-strand breaks (DSBs) in DNA, which are critical lesions that can lead to genomic instability and cancer if not properly repaired.

Function

RAD52 is involved in the homologous recombination repair pathway, which is a high-fidelity mechanism for repairing DSBs. It functions by facilitating the annealing of complementary single-stranded DNA (ssDNA) during the repair process. RAD52 can bind to ssDNA and promote the formation of DNA-DNA interactions, which is essential for the alignment of homologous sequences.

In addition to its role in homologous recombination, RAD52 also participates in the single-strand annealing (SSA) pathway, another mechanism for repairing DSBs. In SSA, RAD52 mediates the annealing of complementary ssDNA regions flanking a DSB, leading to the repair of the break but often resulting in the loss of genetic information between the repeats.

Structure

RAD52 is characterized by its ability to form ring-like oligomeric structures, which are thought to be important for its function in DNA repair. The protein contains a conserved N-terminal domain that is responsible for DNA binding and oligomerization, and a C-terminal domain that interacts with other proteins involved in DNA repair, such as RAD51.

Interactions

RAD52 interacts with several other proteins involved in DNA repair, including RAD51, BRCA2, and RPA (Replication Protein A). These interactions are crucial for the recruitment and stabilization of the repair machinery at sites of DNA damage.

Clinical Significance

Mutations or dysregulation of RAD52 can lead to impaired DNA repair and increased susceptibility to cancer. While RAD52 is not as well-studied as other DNA repair proteins like BRCA1 and BRCA2, it is considered a potential target for cancer therapy, particularly in tumors that are deficient in other homologous recombination repair proteins.

Research

Ongoing research is focused on understanding the precise mechanisms by which RAD52 functions in DNA repair and its potential as a therapeutic target. Studies are also exploring the role of RAD52 in synthetic lethality approaches, where inhibition of RAD52 in cells deficient in other repair pathways could selectively kill cancer cells.

Also see

• DNA repair
• Homologous recombination
• RAD51
• BRCA1
• BRCA2
• Genomic instability