RAD51

RAD51 is a eukaryote is_associated_with::gene. The is_associated_with::protein encoded by this gene is a member of the RAD51 protein family which assist in repair of DNA double strand breaks. RAD51 family members are homologous to the is_associated_with::bacterial is_associated_with::RecA, is_associated_with::Archaeal is_associated_with::RadA and yeast Rad51. The protein is highly conserved in most eukaryotes, from yeast to humans.

Variants
Two alternatively spliced transcript variants of this gene, which encode distinct proteins, have been reported. Transcript variants utilizing alternative polyA signals exist.

Function
In humans, RAD51 is a 339-is_associated_with::amino acid protein that plays a major role in is_associated_with::homologous recombination of DNA during double strand break repair. In this process, an ATP dependent DNA strand exchange takes place in which a template strand invades base-paired strands of homologous DNA molecules. RAD51 is involved in the search for homology and strand pairing stages of the process.

Unlike other proteins involved in DNA metabolism, the RecA/Rad51 family forms a helical nucleoprotein filament on DNA.

This protein can interact with the ssDNA-binding protein RPA, is_associated_with::BRCA2, is_associated_with::PALB2 and is_associated_with::RAD52.

The structural basis for Rad51 filament formation and its functional mechanism still remain poorly understood. However, recent studies using fluorescent labeled Rad51 has indicated that Rad51 fragments elongate via multiple nucleation events followed by growth, with the total fragment terminating when it reaches about 2 μm in length. Disassociation of Rad51 from dsDNA, however, is slow and incomplete, suggesting that there is a separate mechanism that accomplishes this.

Pathology
This protein is also found to interact with is_associated_with::PALB2 and is_associated_with::BRCA2, which may be important for the cellular response to DNA damage. BRCA2 is shown to regulate both the intracellular localization and DNA-binding ability of this protein. Loss of these controls following BRCA2 inactivation may be a key event leading to genomic instability and tumorigenesis.

The Rad51 gene is located on chromosome 15 and several alterations of the gene have been associated with an increased risk of developing is_associated_with::breast cancer. The breast cancer susceptibility protein is_associated_with::BRCA2 and is_associated_with::PALB2 controls the function of Rad51 in the pathway for DNA repair by homologous recombination. Increased RAD51 expression levels have been identified in metastatic canine mammary carcinoma, indicating that genomic instability plays an important role in the carcinogenesis of this tumor type.

Family
In is_associated_with::mammals, seven recA-like genes have been identified: Rad51, Rad51L1/B, Rad51L2/C, Rad51L3/D, is_associated_with::XRCC2, is_associated_with::XRCC3, and DMC1/Lim15. All of these proteins, with the exception of meiosis-specific DMC1, are essential for development in mammals. Rad51 is a member of the RecA-like NTPases.

Interactions
RAD51 has been shown to interact with BRE, RAD54, is_associated_with::RAD54B, is_associated_with::Ataxia telangiectasia mutated, is_associated_with::BRCC3, is_associated_with::BARD1, is_associated_with::BRCA2,           is_associated_with::UBE2I,  is_associated_with::Abl gene, is_associated_with::BRCA1,   is_associated_with::RAD52,  DMC1, is_associated_with::P53  and is_associated_with::Bloom syndrome protein.