RAD51

RAD51 is a human 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 highly similar 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.cite journal | author = Galkin VE, Wu Y, Zhang XP, Qian X, He Y, Yu X, Heyer WD, Luo Y, Egelman EH | title = The Rad51/RadA N-terminal domain activates nucleoprotein filament ATPase activity | journal = Structure | volume = 14 | issue = 6 | pages = 983-92 | year = 2006 | pmid = 16765891 ]

This protein can interact with the ssDNA-binding protein RPA and RAD52.

The structural basis for Rad51 filament formation and its functional mechanism still remain poorly understood.

Pathology

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. [cite journal | author=Daniel DC |title=Highlight: BRCA1 and BRCA2 proteins in breast cancer. |journal=Microsc. Res. Tech. |volume=59 |issue= 1 |pages= 68-83 |year= 2002 |pmid= 12242698 |doi= 10.1002/jemt.10178 ]

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.cite journal | author = Pellegrini L, Yu DS, Lo T, Anand S, Lee M, Blundell TL, Venkitaraman AR | title = Insights into DNA recombination from the structure of a RAD51-BRCA2 complex | journal = Nature | volume = 420 | issue = 6913 | pages = 287-93 | year = 2002 | pmid = 12442171 ]

Family

In mammals, seven recA-like genes have been identified: Rad51, Rad51L1/B, Rad51L2/C, Rad51L3/D, XRCC2, XRCC3, and DMC1/Lim15.cite journal | author = Kawabata M, Kawabata T, Nishibori M |title = Role of recA/RAD51 family proteins in mammals | journal = Acta Med Okayama | volume = 59 | issue = 1 | pages = 1-9 | year = 2005 | pmid = 15902993 ] All of thes proteins, with the exception of meiosis-specific DMC1, are essential for development in mammals.

References

External links

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