RAD51
Rad51 is the eukaryotic homolog of the prokaryotic RecA protein. It is well conserved from yeast to humans.
The protein encoded by this gene is a member of the RAD51 protein family. RAD51 family members are highly similar to bacterial RecA and Saccharomyces cerevisiae Rad51, and are known to be involved in the homologous recombination and repair of DNA. This protein can interact with the ssDNA-binding protein RPA and RAD52, and it is thought to play roles in homologous pairing and strand transfer of DNA. This protein is also found to interact with BRCA1 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. Two alternatively spliced transcript variants of this gene, which encode distinct proteins, have been reported. Transcript variants utilizing alternative polyA signals exist.[2]
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. [3]
The structural basis for Rad51 filament formation and its functional mechanism still remain poorly understood.
Pathology
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 controls the function of Rad51 in the pathway for DNA repair by homologous recombination. [4]
Family
In mammals, seven recA-like genes have been identified: Rad51, Rad51L1/B, Rad51L2/C, Rad51L3/D, XRCC2, XRCC3 and DMC1[5]. Of these, with the exception of meiosis-specific DMC1, are essential for development in mammals.
References
- ↑ [1] Conway, A.B., Lynch, T.W., Zhang, Y., Fortin, G.S., Fung, C.W., Symington, L.S., Rice, P.A. Crystal structure of a Rad51 filament. Nat.Struct.Mol.Biol. v11 pp.791-796, 2004
- ↑ "Entrez Gene: RAD51 RAD51 homolog (RecA homolog, E. coli) (S. cerevisiae)".
- ↑ Galkin,V .E. et al. The Rad51/RadA N-Terminal domain activates nucleoprotein filament ATPase activity. Structure 14, pp. 983-992(2006)
- ↑ Pellegrini, L. et al. Insights into DNA recombination from the structure of a Rad51-BRCA2 complex. Nature 420,287-293(2002)
- ↑ Kawabata,M., Kawabata, T. and Nishibori, M. Role of recA/Rad51 family proteins in mammals. Acta Med.Okayama v59, No.1, pp.1-9(2005)
External links
- RAD51+Protein at the US National Library of Medicine Medical Subject Headings (MeSH)
| Stub icon | This biochemistry article is a stub. You can help Wikipedia by expanding it. |
.svg){kind=link}