BRCA2
Encyclopedia
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.
BRCA2 belongs to the tumor suppressor gene
family and the protein encoded by this gene is involved in the repair of chromosomal
damage with an important role in the error-free repair of DNA
double strand breaks.
The BRCA2 gene is located on the long (q) arm of chromosome 13
at position 12.3 (13q12.3) and is 84,188 base pair
s long.
and BRCA2 genes are very different, at least some functions are interrelated. The protein
s made by both gene
s are essential for repairing damaged DNA. The BRCA2 protein binds to and regulates the protein produced by the RAD51
gene to fix breaks in DNA. These breaks can be caused by natural and medical radiation or other environmental exposures, but also occur when chromosomes exchange genetic material during a special type of cell division that creates sperm and eggs (meiosis
). By repairing DNA, these three proteins play a role in maintaining the stability of the human genome
and prevent dangerous gene rearrangements that can lead to hematologic cancers.
Like BRCA1, BRCA2 probably regulates the activity of other genes and plays a critical role in embryo development.
as part of a hereditary breast-ovarian cancer syndrome. Researchers have identified hundreds of mutations in the BRCA2 gene, many of which cause an increased risk of cancer. BRCA2 mutations are usually insertions or deletions of a small number of DNA base pairs (the building material of chromosomes) in the gene. As a result of these mutations, the protein product of the BRCA2 gene is abnormal and does not function properly. Researchers believe that the defective BRCA2 protein is unable to help fix mutations that occur in other genes. As a result, mutations build up and can cause cells to divide in an uncontrolled way and form a tumor.
People who have two mutated copies of the BRCA2 gene have one type of Fanconi anemia
. This condition is caused by extremely reduced levels of the BRCA2 protein in cells, which allows the accumulation of damaged DNA. Patients with Fanconi anemia are prone to several types of leukemia
(a type of blood cell cancer); solid tumors, particularly of the head, neck, skin, and reproductive organs; and bone marrow suppression
(reduced blood cell production that leads to anemia
). A pathogenic mutation almost anywhere in a model pathway for DNA double strand break repair containing BRCA1 and BRCA2 greatly increases the risks for a subgroup of lymphomas and leukemia.
In addition to breast cancer in men and women, mutations in BRCA2 also lead to an increased risk of ovarian
, Fallopian tube
, prostate
, and pancreatic cancer
s, as well as malignant melanoma. In some studies, mutations in the central part of the gene have been associated with a higher risk of ovarian cancer
and a lower risk of prostate cancer
than mutations in other parts of the gene. Several other types of cancer have also been seen in certain families with BRCA2 mutations.
and Dr Richard Wooster (Institute of Cancer Research
, UK). The Wellcome Trust Sanger Institute (Hinxton, Cambs, UK) collaborated with Stratton and Wooster to isolate the gene. In honour of this discovery and collaboration, the Wellcome Trust has participated in the construction of a cycle path between Addenbrooke's Hospital site in Cambridge and the nearby village of Great Shelford
. It is decorated with over 10,000 lines of 4 colours representing the nucleotide sequence of BRCA2. It makes up part of National Cycle Route 11, and can be seen from trains running between Cambridge and London
.
with
repeat
s that are critical for binding to RAD51
(a key protein in DNA recombinational repair) and resistance to methyl methanesulphonate treatment.
The BRCA2 helical domain adopts a helical structure, consisting of a four-helix cluster core (alpha 1, alpha 8, alpha 9, alpha 10) and two successive beta-hairpins (beta 1 to beta 4). An approximately 50-amino acid segment that contains four short helices
(alpha 2 to alpha 4), meanders around the surface of the core structure
. In BRCA2, the alpha 9 and alpha 10 helices pack with the BRCA2 OB1 domain through van der Waals
contacts involving hydrophobic and aromatic residues, and also through side-chain and backbone hydrogen bonds. This domain binds the 70-amino acid DSS1 (deleted in split-hand/split foot syndrome) protein, which was originally identified as one of three genes
that map to a 1.5-Mb locus
deleted in an inherited developmental malformation syndrome.
The BRCA OB1 domain assumes an OB fold, which consists of a highly curved five-stranded beta-sheet that closes on itself to form a beta-barrel. OB1 has a shallow groove formed by one face of the curved sheet and is demarcated by two loops, one between beta 1 and beta 2 and another between beta 4 and beta 5, which allows for weak single strand DNA binding
. The domain also binds the 70-amino acid DSS1 (deleted in split-hand/split foot syndrome) protein.
The BRCA OB3 domain assumes an OB fold, which consists of a highly curved five-stranded beta-sheet that closes on itself to form a beta-barrel. OB3 has a pronounced groove formed by one face of the curved sheet and is demarcated by two loops, one between beta 1 and beta 2 and another between beta 4 and beta 5, which allows for strong ssDNA binding
.
The Tower domain adopts a secondary structure
consisting of a pair of long, antiparallel
alpha-helices
(the stem) that support a three-helix bundle (3HB) at their end. The 3HB contains a helix-turn-helix
motif and is similar to the DNA binding
domains
of the bacteria
l site-specific recombinases
, and of eukaryotic Myb and homeodomain transcription factor
s. The Tower domain has an important role in the tumour suppressor
function of BRCA2, and is essential for appropriate binding of BRCA2 to DNA.
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...
that in humans is encoded by the BRCA2 gene
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...
.
BRCA2 orthologs have been identified in most mammals for which complete genome data are available.
BRCA2 belongs to the tumor suppressor gene
Tumor suppressor gene
A tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from one step on the path to cancer. When this gene is mutated to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes.-Two-hit hypothesis:Unlike...
family and the protein encoded by this gene is involved in the repair of chromosomal
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
damage with an important role in the error-free repair of DNA
DNA repair
DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many as 1...
double strand breaks.
The BRCA2 gene is located on the long (q) arm of chromosome 13
Chromosome 13 (human)
Chromosome 13 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 13 spans about 114 million base pairs and represents between 3.5 and 4 % of the total DNA in cells....
at position 12.3 (13q12.3) and is 84,188 base pair
Base pair
In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...
s long.
Function
Although the structures of the 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 genes are very different, at least some functions are interrelated. 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...
s made by both gene
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...
s are essential for repairing damaged DNA. The BRCA2 protein binds to and regulates the protein produced by the RAD51
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 homologous to the bacterial RecA and yeast Rad51...
gene to fix breaks in DNA. These breaks can be caused by natural and medical radiation or other environmental exposures, but also occur when chromosomes exchange genetic material during a special type of cell division that creates sperm and eggs (meiosis
Meiosis
Meiosis is a special type of cell division necessary for sexual reproduction. The cells produced by meiosis are gametes or spores. The animals' gametes are called sperm and egg cells....
). By repairing DNA, these three proteins play a role in maintaining the stability of the human genome
Human genome
The human genome is the genome of Homo sapiens, which is stored on 23 chromosome pairs plus the small mitochondrial DNA. 22 of the 23 chromosomes are autosomal chromosome pairs, while the remaining pair is sex-determining...
and prevent dangerous gene rearrangements that can lead to hematologic cancers.
Like BRCA1, BRCA2 probably regulates the activity of other genes and plays a critical role in embryo development.
Clinical significance
Certain variations of the BRCA2 gene cause an increased risk for breast cancerBreast 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...
as part of a hereditary breast-ovarian cancer syndrome. Researchers have identified hundreds of mutations in the BRCA2 gene, many of which cause an increased risk of cancer. BRCA2 mutations are usually insertions or deletions of a small number of DNA base pairs (the building material of chromosomes) in the gene. As a result of these mutations, the protein product of the BRCA2 gene is abnormal and does not function properly. Researchers believe that the defective BRCA2 protein is unable to help fix mutations that occur in other genes. As a result, mutations build up and can cause cells to divide in an uncontrolled way and form a tumor.
People who have two mutated copies of the BRCA2 gene have one type of Fanconi anemia
Fanconi anemia
Fanconi anemia is a genetic disease with an incidence of 1 per 350,000 births, with a higher frequency in Ashkenazi Jews and Afrikaners in South Africa.FA is the result of a genetic defect in a cluster of proteins responsible for DNA repair...
. This condition is caused by extremely reduced levels of the BRCA2 protein in cells, which allows the accumulation of damaged DNA. Patients with Fanconi anemia are prone to several types of leukemia
Leukemia
Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...
(a type of blood cell cancer); solid tumors, particularly of the head, neck, skin, and reproductive organs; and bone marrow suppression
Bone marrow suppression
Bone marrow suppression or myelotoxicity or myelosuppression, is the decrease in cells responsible for providing immunity, carrying oxygen, and those responsible for normal blood clotting is a serious side effect of chemotherapy and certain drugs affecting the immune system such as azathioprine...
(reduced blood cell production that leads to anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
). A pathogenic mutation almost anywhere in a model pathway for DNA double strand break repair containing BRCA1 and BRCA2 greatly increases the risks for a subgroup of lymphomas and leukemia.
In addition to breast cancer in men and women, mutations in BRCA2 also lead to an increased risk of ovarian
Ovarian cancer
Ovarian cancer is a cancerous growth arising from the ovary. Symptoms are frequently very subtle early on and may include: bloating, pelvic pain, difficulty eating and frequent urination, and are easily confused with other illnesses....
, Fallopian tube
Fallopian tube
The Fallopian tubes, also known as oviducts, uterine tubes, and salpinges are two very fine tubes lined with ciliated epithelia, leading from the ovaries of female mammals into the uterus, via the utero-tubal junction...
, prostate
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
, and pancreatic cancer
Pancreatic cancer
Pancreatic cancer refers to a malignant neoplasm of the pancreas. The most common type of pancreatic cancer, accounting for 95% of these tumors is adenocarcinoma, which arises within the exocrine component of the pancreas. A minority arises from the islet cells and is classified as a...
s, as well as malignant melanoma. In some studies, mutations in the central part of the gene have been associated with a higher risk of ovarian cancer
Ovarian cancer
Ovarian cancer is a cancerous growth arising from the ovary. Symptoms are frequently very subtle early on and may include: bloating, pelvic pain, difficulty eating and frequent urination, and are easily confused with other illnesses....
and a lower risk of prostate cancer
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
than mutations in other parts of the gene. Several other types of cancer have also been seen in certain families with BRCA2 mutations.
History
The BRCA2 gene was discovered in 1994 by Professor Michael StrattonMichael Stratton
Professor Michael Rudolf Stratton, FRS is a British clinical scientist and the third Director of the Wellcome Trust Sanger Institute. He currently heads the Cancer Genome Project and is a leader of the International Cancer Genome Consortium.- Career :...
and Dr Richard Wooster (Institute of Cancer Research
Institute of Cancer Research
The Institute of Cancer Research is a cancer research institute located in London, United Kingdom and a constituent college of the federal University of London. The ICR was founded in 1909 as a research department of the Royal Marsden Hospital and joined the University of London in 2003...
, UK). The Wellcome Trust Sanger Institute (Hinxton, Cambs, UK) collaborated with Stratton and Wooster to isolate the gene. In honour of this discovery and collaboration, the Wellcome Trust has participated in the construction of a cycle path between Addenbrooke's Hospital site in Cambridge and the nearby village of Great Shelford
Great Shelford
Great Shelford is a village located approximately four miles to the south of Cambridge, in the county of Cambridgeshire, in eastern England. In 1850 Great Shelford parish contained intersected by the river Cam. The population in 1841 was 803 people...
. It is decorated with over 10,000 lines of 4 colours representing the nucleotide sequence of BRCA2. It makes up part of National Cycle Route 11, and can be seen from trains running between Cambridge and London
West Anglia Main Line
The West Anglia Main Line is one of the two main lines which run from London Liverpool Street, the other being the Great Eastern Main Line. It runs generally north from London, through the towns of Cheshunt, Broxbourne, Harlow, Bishop's Stortford and Audley End station before reaching Cambridge,...
.
Germ line BRCA2 mutations and founder effect
All germ line BRCA2 mutations identified to date have been inherited, suggesting the possibility of a large “founder” effect in which a certain mutation is common to a well-defined population group and can theoretically be traced back to a common ancestor. Given the complexity of mutation screening for BRCA2, these common mutations may simplify the methods required for mutation screening in certain populations. Analysis of mutations that occur with high frequency also permits the study of their clinical expression. A striking example of a founder mutation is found in Iceland, where a single BRCA2 (999del5) mutation accounts for virtually all breast/ovarian cancer families. This frame-shift mutation leads to a highly truncated protein product. In a large study examining hundreds of cancer and control individuals, this 999del5 mutation was found in 0.6% of the general population. Of note, while 72% of patients who were found to be carriers had a moderate or strong family history of breast cancer, 28% had little or no family history of the disease. This strongly suggests the presence of modifying genes that affect the phenotypic expression of this mutation, or possibly the interaction of the BRCA2 mutation with environmental factors. Additional examples of founder mutations in BRCA2 are given in the table below.| Population or subgroup | BRCA2 mutation(s) | Reference(s) |
|---|---|---|
| Ashkenazi Jewish | 6174delT | |
| Dutch | 5579insA | |
| Finns | 8555T>G, 999del5, IVS23-2A>G | |
| French Canadians | 8765delAG | |
| Germans | ||
| Hungarians | 9326insA | |
| Icelandics | 999del5 | |
| Italians | 8765delAG | |
| Northern Irish | 6503delTT | |
| Pakistanis | 3337C>T | |
| Scottish | 6503delTT | |
| Slovenians | IVS16-2A>G | |
| Spanish | 3034delAAAC(codon936), 9254del5 | |
| Swedish | 4486delG |
Interactions
BRCA2 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
- BREBRE (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:...
, - BARD1BARD1BRCA1-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...
, - BCCIPBCCIPBRCA2 and CDKN1A-interacting protein is a protein that in humans is encoded by the BCCIP gene.-Interactions:BCCIP has been shown to interact with BRCA2, P21, and PTPmu -Further reading:...
, - BRCA1BRCA1BRCA1 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...
, - BRCC3BRCC3Lys-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:...
, - BUB1BBUB1BMitotic checkpoint serine/threonine-protein kinase BUB1 beta is an enzyme that in humans is encoded by the BUB1B gene.-Interactions:BUB1B has been shown to interact with AP2B1, HDAC1, BUB3, MAD2L1, Gamma-synuclein, BRCA2 and CDC20.-Further reading:...
, - CREB-binding protein,
- C11orf30C11orf30Protein EMSY is a protein that in humans is encoded by the C11orf30 gene.-Interactions:C11orf30 has been shown to interact with ZMYND11, BRCA2 and CBX1.-Further reading:...
, - FANCD2FANCD2Fanconi anemia group D2 protein is a protein that in humans is encoded by the FANCD2 gene. The Fanconi anemia complementation group currently includes FANCA, FANCB, FANCC, FANCD1 , FANCD2 , FANCE, FANCF, FANCG, and FANCL.- Function :Fanconi anemia is a genetically heterogeneous recessive disorder...
, - FANCGFANCGFanconi anemia group G protein is a protein that in humans is encoded by the FANCG gene.-Interactions:FANCG has been shown to interact with FANCF, FANCA, FANCE and BRCA2.-Further reading:...
, - FLNAFilaminFilamins are a class of proteins that hold two actin filaments at large angles.Types include:* FLNA* FLNB* FLNC...
, - HMG20BHMG20BSWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1-related is a protein that in humans is encoded by the HMG20B gene.-Interactions:...
, - P53P53p53 , 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...
, - PCAFPCAFP300/CBP-associated factor , also known as K acetyltransferase 2B , is a human gene and trancriptional coactivator associated with p53.-Structure:...
, - PLK1PLK1Serine/threonine-protein kinase PLK1, also known as polo-like kinase 1 or serine/threonine-protein kinase 13 , is an enzyme that in humans is encoded by the PLK1 gene.- Structure :...
, - RAD51RAD51RAD51 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 bacterial RecA and yeast Rad51...
, - RPA1,
- SHFM1SHFM126S proteasome complex subunit DSS1 is a protein that in humans is encoded by the SHFM1 gene.-Further reading:...
and - SMAD3Mothers against decapentaplegic homolog 3Mothers against decapentaplegic homolog 3 also known as SMAD family member 3 or SMAD3 is a protein that in humans is encoded by the SMAD3 gene. SMAD3 is a member of the SMAD family of proteins.The human SMAD3 gene is located on chromosome 15...
.
Domain architecture
BRCA2 contains a number of 39 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...
repeat
Tandem repeat
Tandem repeats occur in DNA when a pattern of two or more nucleotides is repeated and the repetitions are directly adjacent to each other. -Example:An example would be:in which the sequence A-T-T-C-G is repeated three times.-Terminology:...
s that are critical for binding to RAD51
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 homologous to the bacterial RecA and yeast Rad51...
(a key protein in DNA recombinational repair) and resistance to methyl methanesulphonate treatment.
The BRCA2 helical domain adopts a helical structure, consisting of a four-helix cluster core (alpha 1, alpha 8, alpha 9, alpha 10) and two successive beta-hairpins (beta 1 to beta 4). An approximately 50-amino acid segment that contains four short helices
Alpha helix
A common motif in the secondary structure of proteins, the alpha helix is a right-handed coiled or spiral conformation, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier...
(alpha 2 to alpha 4), meanders around the surface of the core structure
Secondary structure
In biochemistry and structural biology, secondary structure is the general three-dimensional form of local segments of biopolymers such as proteins and nucleic acids...
. In BRCA2, the alpha 9 and alpha 10 helices pack with the BRCA2 OB1 domain through van der Waals
Van der Waals force
In physical chemistry, the van der Waals force , named after Dutch scientist Johannes Diderik van der Waals, is the sum of the attractive or repulsive forces between molecules other than those due to covalent bonds or to the electrostatic interaction of ions with one another or with neutral...
contacts involving hydrophobic and aromatic residues, and also through side-chain and backbone hydrogen bonds. This domain binds the 70-amino acid DSS1 (deleted in split-hand/split foot syndrome) protein, which was originally identified as one of three genes
Gênes
Gênes is the name of a département of the First French Empire in present Italy, named after the city of Genoa. It was formed in 1805, when Napoleon Bonaparte occupied the Republic of Genoa. Its capital was Genoa, and it was divided in the arrondissements of Genoa, Bobbio, Novi Ligure, Tortona and...
that map to a 1.5-Mb locus
Locus (genetics)
In the fields of genetics and genetic computation, a locus is the specific location of a gene or DNA sequence on a chromosome. A variant of the DNA sequence at a given locus is called an allele. The ordered list of loci known for a particular genome is called a genetic map...
deleted in an inherited developmental malformation syndrome.
The BRCA OB1 domain assumes an OB fold, which consists of a highly curved five-stranded beta-sheet that closes on itself to form a beta-barrel. OB1 has a shallow groove formed by one face of the curved sheet and is demarcated by two loops, one between beta 1 and beta 2 and another between beta 4 and beta 5, which allows for weak single strand DNA binding
Binding (molecular)
Molecular binding is an attractive interaction between two molecules which results in a stable association in which the molecules are in close proximity to each other...
. The domain also binds the 70-amino acid DSS1 (deleted in split-hand/split foot syndrome) protein.
The BRCA OB3 domain assumes an OB fold, which consists of a highly curved five-stranded beta-sheet that closes on itself to form a beta-barrel. OB3 has a pronounced groove formed by one face of the curved sheet and is demarcated by two loops, one between beta 1 and beta 2 and another between beta 4 and beta 5, which allows for strong ssDNA binding
Binding (molecular)
Molecular binding is an attractive interaction between two molecules which results in a stable association in which the molecules are in close proximity to each other...
.
The Tower domain adopts a secondary structure
Secondary structure
In biochemistry and structural biology, secondary structure is the general three-dimensional form of local segments of biopolymers such as proteins and nucleic acids...
consisting of a pair of long, antiparallel
Antiparallel (biochemistry)
In biochemistry, two molecules are antiparallel if they run side-by-side in opposite directions or when both strands are complimentary to each other....
alpha-helices
Alpha helix
A common motif in the secondary structure of proteins, the alpha helix is a right-handed coiled or spiral conformation, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier...
(the stem) that support a three-helix bundle (3HB) at their end. The 3HB contains a helix-turn-helix
Helix-turn-helix
In proteins, the helix-turn-helix is a major structural motif capable of binding DNA. It is composed of two α helices joined by a short strand of amino acids and is found in many proteins that regulate gene expression...
motif and is similar to the DNA binding
Binding (molecular)
Molecular binding is an attractive interaction between two molecules which results in a stable association in which the molecules are in close proximity to each other...
domains
Protein domain
A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...
of 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 site-specific recombinases
Recombinases
Recombinases are genetic recombination enzymes.Types include:* Cre recombinase* Hin recombinase* RecA/RAD51* Tre recombinase* FLP recombinase...
, and of eukaryotic Myb and homeodomain transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
s. The Tower domain has an important role in the tumour suppressor
Tumor suppressor gene
A tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from one step on the path to cancer. When this gene is mutated to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes.-Two-hit hypothesis:Unlike...
function of BRCA2, and is essential for appropriate binding of BRCA2 to DNA.