RAD51

RAD51 recombinase
A filament of Rad51 based on PDB 1SZP.[1]
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1B22, 1N0W
Identifiers
Symbols	RAD51 ; BRCC5; HRAD51; HsRad51; HsT16930; MRMV2; RAD51A; RECA
External IDs	OMIM: 179617 MGI: 97890 HomoloGene: 2155 GeneCards: RAD51 Gene
Gene ontology Molecular function • damaged DNA binding • double-stranded DNA binding • single-stranded DNA binding • protein binding • ATP binding • protein C-terminus binding • identical protein binding • single-stranded DNA-dependent ATPase activity • DNA polymerase binding Cellular component • nuclear chromosome • condensed chromosome • condensed nuclear chromosome • lateral element • nucleus • nucleoplasm • nucleolus • cytoplasm • mitochondrion • mitochondrial matrix • microtubule organizing center • PML body • perinuclear region of cytoplasm Biological process • double-strand break repair via homologous recombination • DNA recombinase assembly • ATP catabolic process • DNA unwinding involved in DNA replication • DNA repair • double-strand break repair • DNA recombination • mitotic recombination • cellular response to DNA damage stimulus • meiotic nuclear division • reciprocal meiotic recombination • regulation of double-strand break repair via homologous recombination • positive regulation of DNA ligation • protein homooligomerization • cellular response to ionizing radiation • cellular response to camptothecin Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5888	19361
Ensembl	ENSG00000051180	ENSMUSG00000027323
UniProt	Q06609	Q08297
RefSeq (mRNA)	NM_001164269	NM_011234
RefSeq (protein)	NP_001157741	NP_035364
Location (UCSC)	Chr 15: 40.99 – 41.02 Mb	Chr 2: 119.11 – 119.15 Mb
PubMed search

RAD51 is a eukaryote gene. The 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 bacterial RecA 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-amino acid protein that plays a major role in 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.^[2]

This protein can interact with the ssDNA-binding protein RPA, BRCA2, PALB2^[3] and RAD52.

The structural basis for Rad51 filament formation and its functional mechanism still remain poorly understood. However, recent studies using fluorescent labeled Rad51^[4] 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 PALB2^[3] and 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.^[5]

The Rad51 gene is located on chromosome 15 and several alterations of the gene have been associated with an increased risk of developing breast cancer. The breast cancer susceptibility protein BRCA2 and PALB2 controls the function of Rad51 in the pathway for DNA repair by homologous recombination.^[3][6] 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.^{[7][8][9][10]}

Family

In mammals, seven recA-like genes have been identified: Rad51, Rad51L1/B, Rad51L2/C, Rad51L3/D, XRCC2, XRCC3, and DMC1/Lim15.^[11] 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,^[12] RAD54,^[13] RAD54B,^[14] Ataxia telangiectasia mutated,^[15] BRCC3,^[12] BARD1,^[12] BRCA2,^{[12][16][17][18][19][20][21][22][6][23][24][25][26]} UBE2I,^[27][28] Abl gene,^[15] BRCA1,^{[12][25][29][30]} RAD52,^[15] DMC1,^[31] P53^[12][32][33] and Bloom syndrome protein.^[34]

References

External links

• RAD51 Protein at the US National Library of Medicine Medical Subject Headings (MeSH)

PDB gallery 1b22: RAD51 (N-TERMINAL DOMAIN)  1n0w: Crystal structure of a RAD51-BRCA2 BRC repeat complex