RAD51
Encyclopedia
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 homologous to the bacteria
l RecA
and yeast
Rad51. The protein is highly conserved in most eukaryotes, from yeast to humans.
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.
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. 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.
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.
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.
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.
, Rad51L2/C
, Rad51L3/D
, XRCC2
, XRCC3
, and DMC1/Lim15. All of these proteins, with the exception of meiosis-specific DMC1, are essential for development in mammals.
with BRE
, RAD54B
, Ataxia telangiectasia mutated
, BRCC3
, BARD1
, BRCA2
, UBE2I
, Abl gene
, BRCA1
, ATRX
, RAD52
, DMC1
, P53
and Bloom syndrome protein
.
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. The protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
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 bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
l RecA
RecA
RecA is a 38 kilodalton Escherichia coli protein essential for the repair and maintenance of DNA. RecA has a structural and functional homolog in every species in which it has been seriously sought and serves as an archetype for this class of homologous DNA repair proteins...
and yeast
Saccharomyces cerevisiae
Saccharomyces cerevisiae is a species of yeast. It is perhaps the most useful yeast, having been instrumental to baking and brewing since ancient times. It is believed that it was originally isolated from the skin of grapes...
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 acidAmino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
protein that plays a major role in homologous recombination
Homologous recombination
Homologous recombination is a type of genetic recombination in which nucleotide sequences are exchanged between two similar or identical molecules of DNA. It is most widely used by cells to accurately repair harmful breaks that occur on both strands of DNA, known as double-strand breaks...
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
Replication protein A
Replication protein A is a protein that binds single-stranded DNA in eukaryotic cells. During DNA replication, RPA prevents single-stranded DNA from winding back on itself or from forming secondary structures. This keeps DNA unwound for the polymerase to replicate it...
and RAD52
RAD52
RAD52 homolog , also known as RAD52, is a protein which in humans is encoded by the RAD52 gene.- Function :The protein encoded by this gene shares similarity with Saccharomyces cerevisiae Rad52, a protein important for DNA double-strand break repair and homologous recombination...
.
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 BRCA1BRCA1
BRCA1 is a human caretaker gene that produces a protein called breast cancer type 1 susceptibility protein, responsible for repairing DNA. The first evidence for the existence of the gene was provided by the King laboratory at UC Berkeley in 1990...
and BRCA2
BRCA2
BRCA2 is a protein that in humans is encoded by the BRCA2 gene.BRCA2 orthologs have been identified in most mammals for which complete genome data are available....
, 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 breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
. The breast cancer susceptibility protein BRCA2
BRCA2
BRCA2 is a protein that in humans is encoded by the BRCA2 gene.BRCA2 orthologs have been identified in most mammals for which complete genome data are available....
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 mammals, seven recA-like genes have been identified: Rad51, Rad51L1/BRAD51L1
DNA repair protein RAD51 homolog 2 is a protein that in humans is encoded by the RAD51L1 gene.-Further reading:...
, Rad51L2/C
RAD51C
RAD51 homolog C , also known as RAD51C, is a protein which in humans is encoded by the RAD51C gene.-Function:This gene is a member of the RAD51 family of related genes, which encode strand-transfer proteins thought to be involved in recombinational repair of damaged DNA and in meiotic recombination...
, Rad51L3/D
RAD51L3
DNA repair protein RAD51 homolog 4 is a protein that in humans is encoded by the RAD51L3 gene.-Interactions:RAD51L3 has been shown to interact with XRCC2, Bloom syndrome protein and RAD51C.-Further reading:...
, XRCC2
XRCC2
DNA repair protein XRCC2 is a protein that in humans is encoded by the XRCC2 gene.-Interactions:XRCC2 has been shown to interact with RAD51L3, Bloom syndrome protein and RAD51C.-Further reading:...
, XRCC3
XRCC3
DNA repair protein XRCC3 is a protein that in humans is encoded by the XRCC3 gene.-Further reading:...
, and DMC1/Lim15. All of these proteins, with the exception of meiosis-specific DMC1, are essential for development in mammals.
Interactions
RAD51 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with BRE
BRE (gene)
BRCA1-A complex subunit BRE is a protein that in humans is encoded by the BRE gene.-Interactions:BRE has been shown to interact with BRCA2, RAD51, BRCC3, BRCA1, C19orf62, P53 and BARD1.-Further reading:...
, RAD54B
RAD54B
DNA repair and recombination protein RAD54B is a protein that in humans is encoded by the RAD54B gene.-Further reading:...
, Ataxia telangiectasia mutated
Ataxia telangiectasia mutated
Ataxia telangiectasia mutated is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks. It phosphorylates several key proteins that initiate activation of the DNA damage checkpoint, leading to cell cycle arrest, DNA repair or apoptosis...
, BRCC3
BRCC3
Lys-63-specific deubiquitinase BRCC36 is an enzyme that in humans is encoded by the BRCC3 gene.-Interactions:BRCC3 has been shown to interact with BRE, BRCA2, RAD51, BRCA1, P53 and BARD1.-Further reading:...
, BARD1
BARD1
BRCA1-associated RING domain protein 1 is a protein that in humans is encoded by the BARD1 gene.-Interactions:BARD1 has been shown to interact with BRE, UBE2D1, CSTF2, BRCC3, RAD51, BCL3, TACC1, Ewing sarcoma breakpoint region 1, FANCD2, H2AFX, CSTF1, NPM1, BRCA2, BRCA1, P53 and Aurora B...
, BRCA2
BRCA2
BRCA2 is a protein that in humans is encoded by the BRCA2 gene.BRCA2 orthologs have been identified in most mammals for which complete genome data are available....
, UBE2I
UBE2I
SUMO-conjugating enzyme UBC9 is a protein that in humans is encoded by the UBE2I gene.-Interactions:UBE2I has been shown to interact with WT1, TOP1, RAD51, Activating transcription factor 2, PIAS1, SALL1, FHIT, RANBP2, Protein inhibitor of activated STAT2, DNMT3A, DNMT3B, Small ubiquitin-related...
, Abl gene
Abl gene
V-abl Abelson murine leukemia viral oncogene homolog 1 also known as ABL1 is a protein that, in humans, is encoded by the ABL1 gene located on chromosome 9.- Function :...
, BRCA1
BRCA1
BRCA1 is a human caretaker gene that produces a protein called breast cancer type 1 susceptibility protein, responsible for repairing DNA. The first evidence for the existence of the gene was provided by the King laboratory at UC Berkeley in 1990...
, ATRX
ATRX
Transcriptional regulator ATRX also known as ATP-dependent helicase ATRX, X-linked helicase II, or X-linked nuclear protein is a protein that in humans is encoded by the ATRX gene.- Function :...
, RAD52
RAD52
RAD52 homolog , also known as RAD52, is a protein which in humans is encoded by the RAD52 gene.- Function :The protein encoded by this gene shares similarity with Saccharomyces cerevisiae Rad52, a protein important for DNA double-strand break repair and homologous recombination...
, DMC1
DMC1 (gene)
Meiotic recombination protein DMC1/LIM15 homolog is a protein that in humans is encoded by the DMC1 gene.-Interactions:DMC1 has been shown to interact with RAD51.-Further reading:...
, P53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
and Bloom syndrome protein
Bloom syndrome protein
Bloom syndrome protein is a protein that in humans is encoded by the BLM gene and is expressed in Bloom syndrome.The Bloom syndrome gene product is related to the RecQ subset of DExH box-containing DNA helicases and has both DNA-stimulated ATPase and ATP-dependent DNA helicase activities...
.