BRCA1 Protein
Genes, BRCA1
BRCA2 Protein
Genes, BRCA2
Germ-Line Mutation
Ovarian Neoplasms
Mutation
Genetic Testing
Heterozygote
Rad51 Recombinase
Genetic Predisposition to Disease
Founder Effect
Breast Neoplasms, Male
Neoplastic Syndromes, Hereditary
Neoplasm Proteins
DNA Repair
Genetic Counseling
DNA Damage
Transcription Factors
Tumor Suppressor Proteins
Pedigree
Ubiquitin-Protein Ligases
Fallopian Tube Neoplasms
Genomic Instability
Phthalazines
Family Health
Mapping the functional domains of BRCA1. Interaction of the ring finger domains of BRCA1 and BARD1. (1/1487)
Breast cancer 1 (BRCA1) and BRCA1-associated RING domain 1 (BARD1) are multidomain proteins that interact in vivo via their N-terminal RING finger motif regions. To characterize functional aspects of the BRCA1/BARD1 interaction, we have defined the structural domains required for the interaction, as well as their oligomerization state, relative stability, and possible nucleic acid binding activity. We have found that the RING finger motifs do not themselves constitute stable structural domains but are instead part of larger domains comprising residues 1-109 of BRCA1 and residues 26-119 of BARD1. These domains exist as homodimers and preferentially form a stable heterodimer. Shorter BRCA1 RING finger constructs do not interact with BARD1 or with longer BRCA1 constructs, indicating that the heterodimeric and homodimer interactions are mediated by regions outside the canonical RING finger motif. Nucleic acid binding is a generally proposed function of RING finger domains. We show that neither the homodimers nor the heterodimer displays affinity for nucleic acids, indicating that the proposed roles of BRCA1 and BARD1 in DNA repair and/or transcriptional activation must be mediated either by other regions of the proteins or by additional cofactors. (+info)Chromatin remodeling and activation of chromosomal DNA replication by an acidic transcriptional activation domain from BRCA1. (2/1487)
An increasing number of transcription factors have been shown to activate DNA replication. However, the underlying mechanism remains to be elucidated. Here it is shown that when tethered to a cellular replication origin, the acidic transcriptional activation domain of the breast cancer protein BRCA1 alters the local chromatin structure and stimulates chromosomal DNA replication. Cancer-predisposing mutations in BRCA1 that abolish transcriptional activation also prevent chromatin remodeling and activation of replication. Chromatin remodeling occurs even in the absence of a functional replication origin. Thus, increasing chromatin accessibility may be an important mechanism used by transcription factors to facilitate multiple nuclear processes. (+info)Should insurance pay for preventive services suggested by genetics? (3/1487)
Physicians, plans and patients are discovering that the promise of genetic testing will be hard to fulfill. Even when a test can show predisposition toward a disease, performing it can't necessarily improve medical outcomes. Unfortunately, doing these tests can have some unintended negative effects. (+info)BRCA1 and BRCA2 proteins: roles in health and disease. (4/1487)
Between 5% and 10% of all breast cancer is hereditary, with patients having a strong family history of the disease. The remaining 90-95% of cases are classed as sporadic. Within the inherited group, 80-90% of cases are the result of germline mutations affecting two recently identified genes: BRCA1 and BRCA2. Since the sequencing of these genes, considerable research on the genetics of the mutation carriers has been performed, with less attention having been focused on the BRCA1 and BRCA2 proteins themselves. The structure and function of the protein products thus continues to hold mystery and might be the key to the full understanding of this complex disease. (+info)Binding of CtIP to the BRCT repeats of BRCA1 involved in the transcription regulation of p21 is disrupted upon DNA damage. (5/1487)
Mutations in BRCA1 are responsible for nearly all of the hereditary ovarian and breast cancers, and about half of those in breast cancer-only kindreds. The ability of BRCA1 to transactivate the p21 promoter can be inactivated by mutation of the conserved BRCA1 C-terminal (BRCT) repeats. To explore the mechanisms of this BRCA1 function, the BRCT repeats were used as bait in a yeast two-hybrid screen. A known protein, CtIP, a co-repressor with CtBP, was found. CtIP interacts specifically with the BRCT repeats of BRCA1, both in vitro and in vivo, and tumor-derived mutations in this region abolished these interactions. The association of BRCA1 with CtIP was also abrogated in cells treated with DNA-damaging agents including UV, gamma-irradiation, and adriamycin, a response correlated with BRCA1 phosphorylation. The transactivation of the p21 promoter by BRCA1 was diminished by expression of exogenous CtIP and CtBP. These results suggest that the binding of the BRCT repeats of BRCA1 to CtIP/CtBP is critical in mediating transcriptional regulation of p21 in response to DNA damage. (+info)Germline BRCA1 alterations in a population-based series of ovarian cancer cases. (6/1487)
The objective of this study was to provide more accurate frequency estimates of breast cancer susceptibility gene 1 ( BRCA1 ) germline alterations in the ovarian cancer population. To achieve this, we determined the prevalence of BRCA1 alterations in a population-based series of consecutive ovarian cancer cases. This is the first population-based ovarian cancer study reporting BRCA1 alterations derived from a comprehensive screen of the entire coding region. One hundred and seven ovarian cancer cases were analyzed for BRCA1 alterations using the RNase mismatch cleavage assay followed by direct sequencing. Two truncating mutations, 962del4 and 3600del11, were identified. Both patients had a family history of breast or ovarian cancer. Several novel as well as previously reported uncharacterized variants were also identified, some of which were associated with a family history of cancer. The frequency distribution of common polymorphisms was determined in the 91 Caucasian cancer cases in this series and 24 sister controls using allele-specific amplification. The rare form of the Q356R polymorphism was significantly ( P = 0.03) associated with a family history of ovarian cancer, suggesting that this polymorphism may influence ovarian cancer risk. In summary, our data suggest a role for some uncharacterized variants and rare forms of polymorphisms in determining ovarian cancer risk, and highlight the necessity to screen for missense alterations as well as truncating mutations in this population. (+info)Centrosome amplification and a defective G2-M cell cycle checkpoint induce genetic instability in BRCA1 exon 11 isoform-deficient cells. (7/1487)
Germline mutations of the Brca1 tumor suppressor gene predispose women to breast and ovarian cancers. To study mechanisms underlying BRCA1-related tumorigenesis, we derived mouse embryonic fibroblast cells carrying a targeted deletion of exon 11 of the Brca1 gene. We show that the mutant cells maintain an intact G1-S cell cycle checkpoint and proliferate poorly. However, a defective G2-M checkpoint in these cells is accompanied by extensive chromosomal abnormalities. Mutant fibroblasts contain multiple, functional centrosomes, which lead to unequal chromosome segregation, abnormal nuclear division, and aneuploidy. These data uncover an essential role of BRCA1 in maintaining genetic stability through the regulation of centrosome duplication and the G2-M checkpoint and provide a molecular basis for the role of BRCA1 in tumorigenesis. (+info)Methylation of the BRCA1 promoter region in sporadic breast and ovarian cancer: correlation with disease characteristics. (8/1487)
Reduced expression of BRCA1 has been reported in sporadic breast cancer, although the mechanisms underlying this phenomenon remain unclear. Abnormal methylation leading to silencing of tumour suppressor genes has been implicated in tumorigenesis in a wide range of sporadic cancers. Therefore, we sought to determine the frequency of methylation within the BRCA1 promoter region in a large group of sporadic invasive breast (n =96) and ovarian (n = 43) carcinomas using Southern analyses. Overall, methylation was detected in 11% of breast cancer cases and in 5% of ovarian tumours. Methylation of the BRCA1 promoter region was strongly correlated with lack of estrogen and progesterone receptor expression. It is clear from the frequency of abnormal methylation of the BRCA1 promoter region, that this cannot be the sole mechanism mediating the reduced expression of BRCA1 that has previously been reported to occur in the majority of invasive sporadic breast tumours. Nevertheless this study suggests that abnormal methylation of the BRCA1 promoter may be important in tumorigenesis in a subset of sporadic breast and ovarian cancers. (+info)BRCA1 protein is a tumor suppressor protein that plays a crucial role in repairing damaged DNA and maintaining genomic stability. The BRCA1 gene provides instructions for making this protein. Mutations in the BRCA1 gene can lead to impaired function of the BRCA1 protein, significantly increasing the risk of developing breast, ovarian, and other types of cancer.
The BRCA1 protein forms complexes with several other proteins to participate in various cellular processes, such as:
1. DNA damage response and repair: BRCA1 helps recognize and repair double-strand DNA breaks through homologous recombination, a precise error-free repair mechanism.
2. Cell cycle checkpoints: BRCA1 is involved in regulating the G1/S and G2/M cell cycle checkpoints to ensure proper DNA replication and cell division.
3. Transcription regulation: BRCA1 can act as a transcriptional co-regulator, influencing the expression of genes involved in various cellular processes, including DNA repair and cell cycle control.
4. Apoptosis: In cases of severe or irreparable DNA damage, BRCA1 helps trigger programmed cell death (apoptosis) to eliminate potentially cancerous cells.
Individuals with inherited mutations in the BRCA1 gene have a higher risk of developing breast and ovarian cancers compared to the general population. Genetic testing for BRCA1 mutations is available for individuals with a family history of these cancers or those who meet specific clinical criteria. Identifying carriers of BRCA1 mutations allows for enhanced cancer surveillance, risk reduction strategies, and potential targeted therapies.
BRCA1 (BReast CAncer gene 1) is a tumor suppressor gene that produces a protein involved in repairing damaged DNA and maintaining genetic stability. Mutations in the BRCA1 gene are associated with an increased risk of developing hereditary breast and ovarian cancers. Inherited mutations in this gene account for about 5% of all breast cancers and about 10-15% of ovarian cancers. Women who have a mutation in the BRCA1 gene have a significantly higher risk of developing breast cancer and ovarian cancer compared to women without mutations. The protein produced by the BRCA1 gene also interacts with other proteins to regulate cell growth and division, so its disruption can lead to uncontrolled cell growth and tumor formation.
BRCA2 (pronounced "braca two") protein is a tumor suppressor protein that plays a crucial role in repairing damaged DNA in cells. It is encoded by the BRCA2 gene, which is located on chromosome 13. Mutations in the BRCA2 gene have been associated with an increased risk of developing certain types of cancer, particularly breast and ovarian cancer in women, and breast and prostate cancer in men.
The BRCA2 protein interacts with other proteins to repair double-strand breaks in DNA through a process called homologous recombination. When the BRCA2 protein is not functioning properly due to a mutation, damaged DNA may not be repaired correctly, leading to genetic instability and an increased risk of cancer.
It's important to note that not all people with BRCA2 mutations will develop cancer, but their risk is higher than those without the mutation. Genetic testing can identify individuals who have inherited a mutation in the BRCA2 gene and help guide medical management and screening recommendations.
BRCA2 is a specific gene that provides instructions for making a protein that helps suppress the growth of cells and plays a crucial role in repairing damaged DNA. Mutations in the BRCA2 gene are known to significantly increase the risk of developing breast cancer, ovarian cancer, and several other types of cancer.
The BRCA2 protein is involved in the process of homologous recombination, which is a type of DNA repair that occurs during cell division. When DNA is damaged, this protein helps to fix the damage by finding a similar sequence on a sister chromatid (a copy of the chromosome) and using it as a template to accurately repair the break.
If the BRCA2 gene is mutated and cannot produce a functional protein, then the cell may not be able to repair damaged DNA effectively. Over time, this can lead to an increased risk of developing cancer due to the accumulation of genetic alterations that cause cells to grow and divide uncontrollably.
It's worth noting that while mutations in the BRCA2 gene are associated with an increased risk of cancer, not everyone who has a mutation will develop cancer. However, those who do develop cancer tend to have an earlier onset and more aggressive form of the disease. Genetic testing can be used to identify mutations in the BRCA2 gene, which can help inform medical management and screening recommendations for individuals and their families.
A germ-line mutation is a genetic change that occurs in the egg or sperm cells (gametes), and thus can be passed down from parents to their offspring. These mutations are present throughout the entire body of the offspring, as they are incorporated into the DNA of every cell during embryonic development.
Germ-line mutations differ from somatic mutations, which occur in other cells of the body that are not involved in reproduction. While somatic mutations can contribute to the development of cancer and other diseases within an individual, they are not passed down to future generations.
It's important to note that germ-line mutations can have significant implications for medical genetics and inherited diseases. For example, if a parent has a germ-line mutation in a gene associated with a particular disease, their offspring may have an increased risk of developing that disease as well.
Breast neoplasms refer to abnormal growths in the breast tissue that can be benign or malignant. Benign breast neoplasms are non-cancerous tumors or growths, while malignant breast neoplasms are cancerous tumors that can invade surrounding tissues and spread to other parts of the body.
Breast neoplasms can arise from different types of cells in the breast, including milk ducts, milk sacs (lobules), or connective tissue. The most common type of breast cancer is ductal carcinoma, which starts in the milk ducts and can spread to other parts of the breast and nearby structures.
Breast neoplasms are usually detected through screening methods such as mammography, ultrasound, or MRI, or through self-examination or clinical examination. Treatment options for breast neoplasms depend on several factors, including the type and stage of the tumor, the patient's age and overall health, and personal preferences. Treatment may include surgery, radiation therapy, chemotherapy, hormone therapy, or targeted therapy.
Ovarian neoplasms refer to abnormal growths or tumors in the ovary, which can be benign (non-cancerous) or malignant (cancerous). These growths can originate from various cell types within the ovary, including epithelial cells, germ cells, and stromal cells. Ovarian neoplasms are often classified based on their cell type of origin, histological features, and potential for invasive or metastatic behavior.
Epithelial ovarian neoplasms are the most common type and can be further categorized into several subtypes, such as serous, mucinous, endometrioid, clear cell, and Brenner tumors. Some of these epithelial tumors have a higher risk of becoming malignant and spreading to other parts of the body.
Germ cell ovarian neoplasms arise from the cells that give rise to eggs (oocytes) and can include teratomas, dysgerminomas, yolk sac tumors, and embryonal carcinomas. Stromal ovarian neoplasms develop from the connective tissue cells supporting the ovary and can include granulosa cell tumors, thecomas, and fibromas.
It is essential to diagnose and treat ovarian neoplasms promptly, as some malignant forms can be aggressive and potentially life-threatening if not managed appropriately. Regular gynecological exams, imaging studies, and tumor marker tests are often used for early detection and monitoring of ovarian neoplasms. Treatment options may include surgery, chemotherapy, or radiation therapy, depending on the type, stage, and patient's overall health condition.
A mutation is a permanent change in the DNA sequence of an organism's genome. Mutations can occur spontaneously or be caused by environmental factors such as exposure to radiation, chemicals, or viruses. They may have various effects on the organism, ranging from benign to harmful, depending on where they occur and whether they alter the function of essential proteins. In some cases, mutations can increase an individual's susceptibility to certain diseases or disorders, while in others, they may confer a survival advantage. Mutations are the driving force behind evolution, as they introduce new genetic variability into populations, which can then be acted upon by natural selection.
I'm sorry for any confusion, but "Jews" is not a medical term. It is a term used to describe a group of people who share cultural, religious, and ethnic heritage. The Jewish people originated from the ancient kingdoms of Israel and Judah. They are bound together by their religion, Judaism, which is based on the Torah, or the five books of Moses.
If you have any medical questions or terms that you would like defined, I'd be happy to help!
Genetic testing is a type of medical test that identifies changes in chromosomes, genes, or proteins. The results of a genetic test can confirm or rule out a suspected genetic condition or help determine a person's chance of developing or passing on a genetic disorder. Genetic tests are performed on a sample of blood, hair, skin, amniotic fluid (the fluid that surrounds a fetus during pregnancy), or other tissue. For example, a physician may recommend genetic testing to help diagnose a genetic condition, confirm the presence of a gene mutation known to increase the risk of developing certain cancers, or determine the chance for a couple to have a child with a genetic disorder.
There are several types of genetic tests, including:
* Diagnostic testing: This type of test is used to identify or confirm a suspected genetic condition in an individual. It may be performed before birth (prenatal testing) or at any time during a person's life.
* Predictive testing: This type of test is used to determine the likelihood that a person will develop a genetic disorder. It is typically offered to individuals who have a family history of a genetic condition but do not show any symptoms themselves.
* Carrier testing: This type of test is used to determine whether a person carries a gene mutation for a genetic disorder. It is often offered to couples who are planning to have children and have a family history of a genetic condition or belong to a population that has an increased risk of certain genetic disorders.
* Preimplantation genetic testing: This type of test is used in conjunction with in vitro fertilization (IVF) to identify genetic changes in embryos before they are implanted in the uterus. It can help couples who have a family history of a genetic disorder or who are at risk of having a child with a genetic condition to conceive a child who is free of the genetic change in question.
* Pharmacogenetic testing: This type of test is used to determine how an individual's genes may affect their response to certain medications. It can help healthcare providers choose the most effective medication and dosage for a patient, reducing the risk of adverse drug reactions.
It is important to note that genetic testing should be performed under the guidance of a qualified healthcare professional who can interpret the results and provide appropriate counseling and support.
A heterozygote is an individual who has inherited two different alleles (versions) of a particular gene, one from each parent. This means that the individual's genotype for that gene contains both a dominant and a recessive allele. The dominant allele will be expressed phenotypically (outwardly visible), while the recessive allele may or may not have any effect on the individual's observable traits, depending on the specific gene and its function. Heterozygotes are often represented as 'Aa', where 'A' is the dominant allele and 'a' is the recessive allele.
Rad51 recombinase is a protein involved in the repair of double-stranded DNA breaks through homologous recombination, a process that helps maintain genomic stability. This protein forms a nucleoprotein filament on single-stranded DNA, facilitating the search for and invasion of homologous sequences in double-stranded DNA. Rad51 recombinase is highly conserved across various species, including humans, and plays a crucial role in preventing genetic disorders, cancer, and aging caused by DNA damage.
Genetic predisposition to disease refers to an increased susceptibility or vulnerability to develop a particular illness or condition due to inheriting specific genetic variations or mutations from one's parents. These genetic factors can make it more likely for an individual to develop a certain disease, but it does not guarantee that the person will definitely get the disease. Environmental factors, lifestyle choices, and interactions between genes also play crucial roles in determining if a genetically predisposed person will actually develop the disease. It is essential to understand that having a genetic predisposition only implies a higher risk, not an inevitable outcome.
The Founder Effect is a concept in population genetics that refers to the loss of genetic variation that occurs when a new colony is established by a small number of individuals from a larger population. This decrease in genetic diversity can lead to an increase in homozygosity, which can in turn result in a higher frequency of certain genetic disorders or traits within the founding population and its descendants. The Founder Effect is named after the "founding" members of the new colony who carry and pass on their particular set of genes to the next generations. It is one of the mechanisms that can lead to the formation of distinct populations or even new species over time.
Breast neoplasms in males refer to abnormal growths or tumors in the male breast tissue. These neoplasms can be benign (non-cancerous) or malignant (cancerous). While breast cancer is much less common in men than in women, it can still occur and should be taken seriously.
The most common type of breast cancer in men is invasive ductal carcinoma, which starts in the milk ducts and spreads to surrounding tissue. Other types of breast cancer that can occur in men include inflammatory breast cancer, lobular carcinoma, and Paget's disease of the nipple.
Risk factors for developing male breast cancer include age (most cases are diagnosed after age 60), family history of breast cancer, genetic mutations such as BRCA1 or BRCA2, radiation exposure, obesity, liver disease, and testicular conditions such as undescended testicles.
Symptoms of male breast neoplasms may include a painless lump in the breast tissue, skin changes such as dimpling or redness, nipple discharge, or a retracted nipple. If you notice any of these symptoms, it is important to consult with a healthcare professional for further evaluation and treatment.
Hereditary neoplastic syndromes refer to genetic disorders that predispose affected individuals to develop tumors or cancers. These syndromes are caused by inherited mutations in specific genes that regulate cell growth and division. As a result, cells may divide and grow uncontrollably, leading to the formation of benign or malignant tumors.
Examples of hereditary neoplastic syndromes include:
1. Hereditary breast and ovarian cancer syndrome (HBOC): This syndrome is caused by mutations in the BRCA1 or BRCA2 genes, which increase the risk of developing breast, ovarian, and other cancers.
2. Lynch syndrome: Also known as hereditary non-polyposis colorectal cancer (HNPCC), this syndrome is caused by mutations in DNA mismatch repair genes, leading to an increased risk of colon, endometrial, and other cancers.
3. Li-Fraumeni syndrome: This syndrome is caused by mutations in the TP53 gene, which increases the risk of developing a wide range of cancers, including breast, brain, and soft tissue sarcomas.
4. Familial adenomatous polyposis (FAP): This syndrome is caused by mutations in the APC gene, leading to the development of numerous colon polyps that can become cancerous if not removed.
5. Neurofibromatosis type 1 (NF1): This syndrome is caused by mutations in the NF1 gene and is characterized by the development of benign tumors called neurofibromas on the nerves and skin.
6. Von Hippel-Lindau disease (VHL): This syndrome is caused by mutations in the VHL gene, leading to an increased risk of developing various types of tumors, including kidney, pancreas, and adrenal gland tumors.
Individuals with hereditary neoplastic syndromes often have a higher risk of developing cancer than the general population, and they may require more frequent screening and surveillance to detect cancers at an early stage when they are more treatable.
A neoplasm is a tumor or growth that is formed by an abnormal and excessive proliferation of cells, which can be benign or malignant. Neoplasm proteins are therefore any proteins that are expressed or produced in these neoplastic cells. These proteins can play various roles in the development, progression, and maintenance of neoplasms.
Some neoplasm proteins may contribute to the uncontrolled cell growth and division seen in cancer, such as oncogenic proteins that promote cell cycle progression or inhibit apoptosis (programmed cell death). Others may help the neoplastic cells evade the immune system, allowing them to proliferate undetected. Still others may be involved in angiogenesis, the formation of new blood vessels that supply the tumor with nutrients and oxygen.
Neoplasm proteins can also serve as biomarkers for cancer diagnosis, prognosis, or treatment response. For example, the presence or level of certain neoplasm proteins in biological samples such as blood or tissue may indicate the presence of a specific type of cancer, help predict the likelihood of cancer recurrence, or suggest whether a particular therapy will be effective.
Overall, understanding the roles and behaviors of neoplasm proteins can provide valuable insights into the biology of cancer and inform the development of new diagnostic and therapeutic strategies.
DNA Mutational Analysis is a laboratory test used to identify genetic variations or changes (mutations) in the DNA sequence of a gene. This type of analysis can be used to diagnose genetic disorders, predict the risk of developing certain diseases, determine the most effective treatment for cancer, or assess the likelihood of passing on an inherited condition to offspring.
The test involves extracting DNA from a patient's sample (such as blood, saliva, or tissue), amplifying specific regions of interest using polymerase chain reaction (PCR), and then sequencing those regions to determine the precise order of nucleotide bases in the DNA molecule. The resulting sequence is then compared to reference sequences to identify any variations or mutations that may be present.
DNA Mutational Analysis can detect a wide range of genetic changes, including single-nucleotide polymorphisms (SNPs), insertions, deletions, duplications, and rearrangements. The test is often used in conjunction with other diagnostic tests and clinical evaluations to provide a comprehensive assessment of a patient's genetic profile.
It is important to note that not all mutations are pathogenic or associated with disease, and the interpretation of DNA Mutational Analysis results requires careful consideration of the patient's medical history, family history, and other relevant factors.
DNA repair is the process by which cells identify and correct damage to the DNA molecules that encode their genome. DNA can be damaged by a variety of internal and external factors, such as radiation, chemicals, and metabolic byproducts. If left unrepaired, this damage can lead to mutations, which may in turn lead to cancer and other diseases.
There are several different mechanisms for repairing DNA damage, including:
1. Base excision repair (BER): This process repairs damage to a single base in the DNA molecule. An enzyme called a glycosylase removes the damaged base, leaving a gap that is then filled in by other enzymes.
2. Nucleotide excision repair (NER): This process repairs more severe damage, such as bulky adducts or crosslinks between the two strands of the DNA molecule. An enzyme cuts out a section of the damaged DNA, and the gap is then filled in by other enzymes.
3. Mismatch repair (MMR): This process repairs errors that occur during DNA replication, such as mismatched bases or small insertions or deletions. Specialized enzymes recognize the error and remove a section of the newly synthesized strand, which is then replaced by new nucleotides.
4. Double-strand break repair (DSBR): This process repairs breaks in both strands of the DNA molecule. There are two main pathways for DSBR: non-homologous end joining (NHEJ) and homologous recombination (HR). NHEJ directly rejoins the broken ends, while HR uses a template from a sister chromatid to repair the break.
Overall, DNA repair is a crucial process that helps maintain genome stability and prevent the development of diseases caused by genetic mutations.
Genetic counseling is a process of communication and education between a healthcare professional and an individual or family, aimed at understanding, adapting to, and managing the medical, psychological, and familial implications of genetic contributions to disease. This includes providing information about the risk of inherited conditions, explaining the implications of test results, discussing reproductive options, and offering support and resources for coping with a genetic condition. Genetic counselors are trained healthcare professionals who specialize in helping people understand genetic information and its impact on their health and lives.
DNA damage refers to any alteration in the structure or composition of deoxyribonucleic acid (DNA), which is the genetic material present in cells. DNA damage can result from various internal and external factors, including environmental exposures such as ultraviolet radiation, tobacco smoke, and certain chemicals, as well as normal cellular processes such as replication and oxidative metabolism.
Examples of DNA damage include base modifications, base deletions or insertions, single-strand breaks, double-strand breaks, and crosslinks between the two strands of the DNA helix. These types of damage can lead to mutations, genomic instability, and chromosomal aberrations, which can contribute to the development of diseases such as cancer, neurodegenerative disorders, and aging-related conditions.
The body has several mechanisms for repairing DNA damage, including base excision repair, nucleotide excision repair, mismatch repair, and double-strand break repair. However, if the damage is too extensive or the repair mechanisms are impaired, the cell may undergo apoptosis (programmed cell death) to prevent the propagation of potentially harmful mutations.
Salpingectomy is a surgical procedure in which one or both of the fallopian tubes are removed. These tubes are slender structures that connect the ovaries to the uterus, through which the egg travels from the ovary to the uterus during ovulation. Salpingectomy can be performed for various reasons such as ectopic pregnancy, salpingitis (inflammation of the fallopian tubes), hydrosalpinx (fluid-filled tube), or as a preventative measure in women with increased risk of ovarian cancer. The procedure can be carried out through laparoscopy, hysteroscopy, or laparotomy, depending on the patient's condition and the surgeon's preference.
Transcription factors are proteins that play a crucial role in regulating gene expression by controlling the transcription of DNA to messenger RNA (mRNA). They function by binding to specific DNA sequences, known as response elements, located in the promoter region or enhancer regions of target genes. This binding can either activate or repress the initiation of transcription, depending on the properties and interactions of the particular transcription factor. Transcription factors often act as part of a complex network of regulatory proteins that determine the precise spatiotemporal patterns of gene expression during development, differentiation, and homeostasis in an organism.
Tumor suppressor proteins are a type of regulatory protein that helps control the cell cycle and prevent cells from dividing and growing in an uncontrolled manner. They work to inhibit tumor growth by preventing the formation of tumors or slowing down their progression. These proteins can repair damaged DNA, regulate gene expression, and initiate programmed cell death (apoptosis) if the damage is too severe for repair.
Mutations in tumor suppressor genes, which provide the code for these proteins, can lead to a decrease or loss of function in the resulting protein. This can result in uncontrolled cell growth and division, leading to the formation of tumors and cancer. Examples of tumor suppressor proteins include p53, Rb (retinoblastoma), and BRCA1/2.
Homologous recombination is a type of genetic recombination that occurs between two similar or identical (homologous) segments of DNA. It is a natural process that helps to maintain the stability of an organism's genome and plays a crucial role in DNA repair, particularly the repair of double-strand breaks.
In homologous recombination, the two DNA molecules exchange genetic information through a series of steps, including the formation of Holliday junctions, where the strands cross over and exchange partners. This process can result in new combinations of genetic material, which can increase genetic diversity and contribute to evolution.
Homologous recombination is also used in biotechnology and genetic engineering to introduce specific changes into DNA sequences or to create genetically modified organisms.
I must clarify that the term "pedigree" is not typically used in medical definitions. Instead, it is often employed in genetics and breeding, where it refers to the recorded ancestry of an individual or a family, tracing the inheritance of specific traits or diseases. In human genetics, a pedigree can help illustrate the pattern of genetic inheritance in families over multiple generations. However, it is not a medical term with a specific clinical definition.
Ubiquitin-protein ligases, also known as E3 ubiquitin ligases, are a group of enzymes that play a crucial role in the ubiquitination process. Ubiquitination is a post-translational modification where ubiquitin molecules are attached to specific target proteins, marking them for degradation by the proteasome or for other regulatory functions.
Ubiquitin-protein ligases catalyze the final step in this process by binding to both the ubiquitin protein and the target protein, facilitating the transfer of ubiquitin from an E2 ubiquitin-conjugating enzyme to the target protein. There are several different types of ubiquitin-protein ligases, each with their own specificity for particular target proteins and regulatory functions.
Ubiquitin-protein ligases have been implicated in various cellular processes such as protein degradation, DNA repair, signal transduction, and regulation of the cell cycle. Dysregulation of ubiquitination has been associated with several diseases, including cancer, neurodegenerative disorders, and inflammatory responses. Therefore, understanding the function and regulation of ubiquitin-protein ligases is an important area of research in biology and medicine.
Fallopian tube neoplasms are abnormal growths that occur in the epithelial lining of the fallopian tubes, which are a pair of narrow tubes that transport eggs from the ovaries to the uterus during ovulation. These neoplasms can be benign (non-cancerous) or malignant (cancerous).
Benign neoplasms of the fallopian tube include adenomas, papillomas, and leiomyomas. They are usually asymptomatic but can cause symptoms such as pelvic pain, abnormal vaginal bleeding, and infertility. Treatment typically involves surgical removal of the neoplasm.
Malignant neoplasms of the fallopian tube are rare and include primary fallopian tube carcinoma and metastatic tumors that have spread to the fallopian tubes from other organs. Primary fallopian tube carcinoma is a highly aggressive cancer that can cause symptoms such as abnormal vaginal bleeding, pelvic pain, and watery discharge. Treatment typically involves surgical removal of the affected tube, followed by chemotherapy and radiation therapy.
Overall, Fallopian tube neoplasms are uncommon but can have serious consequences if left untreated. Regular gynecological exams and screenings can help detect these neoplasms early and improve treatment outcomes.
Genomic instability is a term used in genetics and molecular biology to describe a state of increased susceptibility to genetic changes or mutations in the genome. It can be defined as a condition where the integrity and stability of the genome are compromised, leading to an increased rate of DNA alterations such as point mutations, insertions, deletions, and chromosomal rearrangements.
Genomic instability is a hallmark of cancer cells and can also be observed in various other diseases, including genetic disorders and aging. It can arise due to defects in the DNA repair mechanisms, telomere maintenance, epigenetic regulation, or chromosome segregation during cell division. These defects can result from inherited genetic mutations, acquired somatic mutations, exposure to environmental mutagens, or age-related degenerative changes.
Genomic instability is a significant factor in the development and progression of cancer as it promotes the accumulation of oncogenic mutations that contribute to tumor initiation, growth, and metastasis. Therefore, understanding the mechanisms underlying genomic instability is crucial for developing effective strategies for cancer prevention, diagnosis, and treatment.
Heterozygote detection is a method used in genetics to identify individuals who carry one normal and one mutated copy of a gene. These individuals are known as heterozygotes and they do not typically show symptoms of the genetic disorder associated with the mutation, but they can pass the mutated gene on to their offspring, who may then be affected.
Heterozygote detection is often used in genetic counseling and screening programs for recessive disorders such as cystic fibrosis or sickle cell anemia. By identifying heterozygotes, individuals can be informed of their carrier status and the potential risks to their offspring. This information can help them make informed decisions about family planning and reproductive options.
Various methods can be used for heterozygote detection, including polymerase chain reaction (PCR) based tests, DNA sequencing, and genetic linkage analysis. The choice of method depends on the specific gene or mutation being tested, as well as the availability and cost of the testing technology.
Phthalazines are not a medical term, but a chemical one. They refer to a class of heterocyclic organic compounds that contain a phthalazine ring in their structure. The phthalazine ring is made up of two benzene rings fused to a single six-membered saturated carbon ring containing two nitrogen atoms.
Phthalazines have no specific medical relevance, but some of their derivatives are used in the pharmaceutical industry as building blocks for various drugs. For example, certain phthalazine derivatives have been developed as potential medications for conditions such as hypertension, heart failure, and cancer. However, these compounds are still in the experimental stages and have not yet been approved for medical use.
It's worth noting that some phthalazines have been found to have toxic effects on living organisms, so their use in medical applications is carefully regulated.
"Family Health" is not a term that has a single, widely accepted medical definition. However, in the context of healthcare and public health, "family health" often refers to the physical, mental, and social well-being of all members of a family unit. It includes the assessment, promotion, and prevention of health conditions that affect individual family members as well as the family as a whole.
Family health may also encompass interventions and programs that aim to strengthen family relationships, communication, and functioning, as these factors can have a significant impact on overall health outcomes. Additionally, family health may involve addressing social determinants of health, such as poverty, housing, and access to healthcare, which can affect the health of families and communities.
Overall, family health is a holistic approach to healthcare that recognizes the importance of considering the needs and experiences of all family members in promoting and maintaining good health.
A cell line that is derived from tumor cells and has been adapted to grow in culture. These cell lines are often used in research to study the characteristics of cancer cells, including their growth patterns, genetic changes, and responses to various treatments. They can be established from many different types of tumors, such as carcinomas, sarcomas, and leukemias. Once established, these cell lines can be grown and maintained indefinitely in the laboratory, allowing researchers to conduct experiments and studies that would not be feasible using primary tumor cells. It is important to note that tumor cell lines may not always accurately represent the behavior of the original tumor, as they can undergo genetic changes during their time in culture.
Neoplastic gene expression regulation refers to the processes that control the production of proteins and other molecules from genes in neoplastic cells, or cells that are part of a tumor or cancer. In a normal cell, gene expression is tightly regulated to ensure that the right genes are turned on or off at the right time. However, in cancer cells, this regulation can be disrupted, leading to the overexpression or underexpression of certain genes.
Neoplastic gene expression regulation can be affected by a variety of factors, including genetic mutations, epigenetic changes, and signals from the tumor microenvironment. These changes can lead to the activation of oncogenes (genes that promote cancer growth and development) or the inactivation of tumor suppressor genes (genes that prevent cancer).
Understanding neoplastic gene expression regulation is important for developing new therapies for cancer, as targeting specific genes or pathways involved in this process can help to inhibit cancer growth and progression.
BRCA1
BRAP (gene)
RBBP8
RAD51
FANCA
USF2
CDS1 (gene)
BRIP1
FHL2
RBBP7
Tumor suppressor gene
Rad50
Nibrin
MED17
Proximity ligation assay
MRE11A
POLR2A
Nucleolar and spindle associated protein 1
BAP1
Cruciform DNA
Fanconi anemia, complementation group C
FANCD2
PEG3
60S ribosomal protein L31
FANCE
FANCG
WNT2B
PALB2
FLNA
Microcephalin
Brap MGI Mouse Gene Detail - MGI:1919649 - BRCA1 associated protein
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2020-2021 BCSC Basic and Clinical Science Course™
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Poly(ADP-ribose) polymerase-1 antagonizes DNA resection at double-strand breaks | Nature Communications
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Carla SCHMIDT | Group Leader | Professor | Johannes Gutenberg-Universität Mainz, Mainz | JGU | Research profile
DNA Recombination
Mutations27
- Methods to test for the likelihood of a patient with mutations in BRCA1 and BRCA2 developing cancer were covered by patents owned or controlled by Myriad Genetics. (wikipedia.org)
- Furthermore, Rdd-BRCA1 protein expression was detected in recurrent carcinomas from patients who carried germline BRCA1 185delAG mutations. (jci.org)
- Germline loss-of-function mutations in BRCA1 are associated with a high lifetime risk of breast and ovarian cancer. (biomedcentral.com)
- Most mutations in the gene are 'truncating': in the main these induce premature termination codons, resulting in nonsense-mediated decay, loss of the transcript and/or the entire protein. (biomedcentral.com)
- These are chiefly missense mutations, introducing an amino acid change in the context of an expressed protein. (biomedcentral.com)
- INTRODUCTION: Interpretation of results from mutation screening of tumour suppressor genes known to harbour high risk susceptibility mutations, such as APC, BRCA1 , BRCA2 , MLH1 , MSH2 , TP53 , and PTEN , is becoming an increasingly important part of clinical practice. (xenbase.org)
- Understanding missense mutations in the BRCA1 gene: an evolutionary approach. (xenbase.org)
- Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk. (xenbase.org)
- BRCA1 mutations in primary breast and ovarian carcinomas. (xenbase.org)
- So when you have a mutation in BRCA1 and BRCA2 you can't fix damage and you get a lot of mutations in your genome. (thenakedscientists.com)
- Population-based estimate of the average age-specific cumulative risk of breast cancer for a defined set of protein-truncating mutations in BRCA1 and BRCA2. (cancervic.org.au)
- 11- 13 The finding of breast cancer associated mutations within the RING finger domain of BRCA1 , disrupting BRCA1/BARD1 interaction, 11, 14 and the occurrence of BARD1 missense mutations in breast cancer patients, 15- 17 implies participation of BARD1 in BRCA1 mediated tumour suppression. (bmj.com)
- Although inherited mutations in a small number of genes account for only about five to ten percent of women's cancers, by far the BRCA1 and BRCA2 gene mutations are the most common examples of this observation (50-70% of familial breast cancers) [ 2 ]. (hindawi.com)
- We are investigating the impact of specific classes of gene mutations, such as ATM, BRCA1, and MYBL2 on genome integrity. (birmingham.ac.uk)
- Dr. Ryan Jensen, one of the world's leading experts on the tumor-suppressing BRCA1 and BRCA2 genes, is constructing a model to uncover how mutations in these genes lead to cancer. (yale.edu)
- Mutations on the BRCA1 gene and the similarly tumor-suppressing BRCA2 gene also carry increased lifetime risk for cancers of the pancreas and prostate. (yale.edu)
- Currently, genetic laboratories can look for well-established disease-causing mutations in specific populations, such as Ashkenazi Jews, who are more likely to pass on any of two clearly defined mutations of the BRCA1 gene or one particular mutation of the BRCA2 gene. (yale.edu)
- However, even five years after Jolie's announcement, it remains unclear what causes the 95% of total breast cancer cases unrelated to BRCA1/2 mutations. (yale.edu)
- Genetic testing for deleterious mutations in breast cancer 1, early onset gene ( BRCA1 ) and BRCA2 can provide key information to guide clinical decision making. (jci.org)
- In the clinic, genetic testing for BRCA1 and BRCA2 mutations is offered to women in high-risk families and yields one of several possible results. (jci.org)
- OBJECTIVE: To determine prevalence of known disease-related mutations and other variants in BRCA1 and how it differs by race, age at diagnosis, and family history status in a population-based sample of white and black patients with breast cancer unselected for family history. (duke.edu)
- RESULTS: Three of 211 patients with breast cancer had disease-related variants at BRCA1, all of which were protein-truncating mutations. (duke.edu)
- In contrast, BRCA1 mutations are sufficiently frequent in families with both breast and ovarian cancer, or at least 4 cases of breast cancer (at any age), that genotyping might be considered. (duke.edu)
- Scope includes mutations and abnormal protein expression. (cancerindex.org)
- Previous studies have reported variation in BRCA1 breast and ovarian cancer risks with mutation position, suggesting that mutations toward the 3' end of the gene are associated with lower ovarian cancer risks. (lu.se)
- We evaluated the evidence for genotype-phenotype correlations in 356 families with protein-truncating BRCA1 mutations. (lu.se)
- The cancer risks associated with missense mutations in the RING domain in exon 5 appear to be similar to those associated with protein-truncating mutations toward the 3' end of BRCA1, based on nine additional families. (lu.se)
Genes15
- The NEBNext Direct BRCA1/BRCA2 Panel is designed to enrich for the complete exonic content of the BRCA1 and BRCA2 genes. (neb.com)
- This histogram shows the normalized mean coverage across each of the 49 exon targets of the BRCA1 and BRCA2 genes. (neb.com)
- Researchers have linked a number of genes, including BRCA1 and BRCA2, to the development of breast cancer. (medicalnewstoday.com)
- BRCA1 and BRCA2 are tumor suppressor genes. (medicalnewstoday.com)
- A change in this gene results in a protein that interacts with the BRCA1 and BRCA2 genes. (medicalnewstoday.com)
- Yarden's lab discovered that BRCA1 targets two specific proteins cyclin B and Cdc25c, which are the "keeper genes" that regulate the G2/M checkpoint - the last checkpoint a cell has to go through before it divides. (georgetown.edu)
- Approximately 5-10% of all breast and ovarian cancers are thought to arise from a hereditary predisposition to the disease, 1 BRCA1 and BRCA2 being the most important susceptibility genes. (bmj.com)
- 8- 10 In attempts to identify new breast and ovarian cancer susceptibility genes, much research has focused on BRCA1 associated proteins. (bmj.com)
- Examples of these genes are BRCA1 and BRCA2 in breast and ovarian cancers. (hindawi.com)
- In fact, there are thousands of mostly benign variants in BRCA1/2 genes, more accurately called either benign polymorphisms or variants of uncertain significance (or VUS). (yale.edu)
- His research may also help to explain why patients who inherit faulty BRCA1 and BRCA2 genes are more predisposed to breast cancer. (againstbreastcancer.org.uk)
- The BRCA1/2 genes work to correct potential tumor-causing mistakes made during the replication of DNA, the material carrying the body's genetic code that directs the production of proteins and passes traits from parents to offspring. (yale.edu)
- Sequence analysis of these genes is being used to identify BRCA1/2 mutation carriers, though these efforts are hampered by the high frequency of variants of unknown clinical significance (VUSs). (jci.org)
- A focused survey of BRCA1 regulated genes in prostate carcinoma reveals that multiple regulators of genome stability and cell cycle control, including: BLM, FEN1, DDB2, H3F3B, BRCA2, CCNB2, MAD2L1 and GADD153, are direct transcriptional targets of BRCA1. (conicet.gov.ar)
- Study of the Genetic Variants in BRCA1/2 and Non-BRCA Genes in a Population-Based Cohort of 2155 Breast/Ovary Cancer Patients, Including 443 Triple-Negative Breast Cancer Patients, in Argentina. (cdc.gov)
Cancers3
- The findings, published online today in Oncogene , focus on the gene BRCA1, which is mutated in a majority of families who have hereditary breast and/or ovarian cancers, according to senior author Ronit I. Yarden, PhD , assistant professor in the department of human science at the School of Nursing & Health Studies . (georgetown.edu)
- 2, 3 Genomic alterations in BRCA1 are found in 40-50% of families with a high incidence of breast cancer (six or more cases), and in a majority (75-80%) of the families that display both breast and ovarian cancers. (bmj.com)
- We recently discovered new ways the BRCA1 gene functions which could help expand our understanding of the development of ovarian and breast cancers. (birmingham.ac.uk)
Variants17
- The improved screening methods now in use across the UK will identify many carriers of unclassified BRCA1 variants. (biomedcentral.com)
- Indeed more than one-quarter of entries recorded in the Breast Cancer Information Core dataset of BRCA1 sequence variants collected from patients worldwide are unclassified missense alterations http://research.nhgri.nih.gov/bic/ . (biomedcentral.com)
- We have shown that experimental missense variants, generated randomly and selected for loss of interaction with the BRCA1 ubiquitin ligase components, BARD1 and the E2 enzyme UbcH5, identify variants reported within the Breast Cancer Information Core database of individuals with a personal or family history of breast cancer [ 4 ]. (biomedcentral.com)
- The E2 component is particularly sensitive to missense alteration in BRCA1, with the majority of currently unclassified variants in the region inhibiting interaction, whereas the BARD1 component is disrupted by a smaller, but overlapping, subset restricted to substitution of the structurally detrimental zinc-ligation residues. (biomedcentral.com)
- Using yeast two-hybrid analysis for BRCA1:BARD1 and BRCA1:E2 interaction, we have tested the most chemically different substitutions achievable by single nucleotide change in all of the most highly conserved amino acids of the region (invariant from human to sea urchin), and have also tested all currently identified patient missense variants. (biomedcentral.com)
- Goldgar DE, Easton DF, Deffenbaugh AM, Monteiro AN, Tavtigian SV, Couch FJ: Integrated evaluation of DNA sequence variants of unknown clinical significance: application to BRCA1 and BRCA2. (biomedcentral.com)
- The BRCA1/BRCA2 panel demonstrates extremely high specificity and unmatched coverage uniformity across a wide range of DNA inputs, allowing highly sensitive calling of germline and somatic variants while maximizing sequencer efficiency. (neb.com)
- METHODS: We have used a combination of a multiple sequence alignment of orthologous BRCA1 sequences and a measure of the chemical difference between the amino acids present at individual residues in the sequence alignment to classify missense variants and in-frame deletions detected during mutation screening of BRCA1 . (xenbase.org)
- Thus we have tentatively classified about 50% of the unclassified missense variants observed during clinical testing of BRCA1 . (xenbase.org)
- Characterization of common BRCA1 and BRCA2 variants. (xenbase.org)
- Treatment decisions following genetic testing classified as a BRCA1 or BRCA2 variant of uncertain significance are based on probabilistic models, not specific risk associated with a patient's particular variant or variants. (yale.edu)
- In this study we developed a functional assay using mouse ES cells to study variants of BRCA1. (jci.org)
- We introduced BAC clones with human wild-type BRCA1 or variants into Brca1-null ES cells and confirmed that only wild-type and a known neutral variant rescued cell lethality. (jci.org)
- Furthermore, we used this assay to determine the effects of BRCA1 variants on cell cycle regulation, differentiation, and genomic stability. (jci.org)
- Our results demonstrate that this ES cell-based assay is a powerful and reliable method for analyzing the functional impact of BRCA1 variants, which we believe could be used to determine which patients may require preventative treatments. (jci.org)
- This strategy should provide new avenues for clinicians to interpret results of genetic testing of BRCA1 variants and for researchers to study the basic molecular mechanisms of BRCA1 function in in vivo model systems. (jci.org)
- MAIN OUTCOME MEASURE: Germline variants at any site in the coding sequence, splice junctions, 5' untranslated region, or 3' untranslated region of the BRCA1 gene were analyzed in cases, and selected variants were analyzed in controls. (duke.edu)
Interacts4
- The BRCA1 protein associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase complexes. (wikipedia.org)
- This RING domain interacts with associated proteins, including BARD1, which also contains a RING motif, to form a heterodimer. (wikipedia.org)
- 6, 7 BRCA1 interacts with a variety of proteins and is involved in multiple cellular processes including DNA repair, transcription, and checkpoint control. (bmj.com)
- BACH1, a novel helicase-like protein, interacts directly with BRCA1 and contributes to its DNA repair function. (umassmed.edu)
RAD515
- Functionally, Rdd-BRCA1 formed irradiation-induced foci and supported RAD51 foci formation. (jci.org)
- B ) SUM1315MO2 parental, RR1-3, and CR1-3 cells were treated with IR, and BRCA1, RAD51, γ-H2AX, and DAPI were detected by immunofluorescence (representative images are shown). (jci.org)
- By mechanism, DNA annealing proteins are divided into ATPases capable of strand invasion (RecA, RAD51) and single strand annealing proteins (SSAPs) that do not utilize ATP 4 . (nature.com)
- Surprisingly, despite anticipated defects in DNA binding or RAD51-mediated DNA strand exchange, the BRCA2 R3052W protein mislocalizes to the cytoplasm precluding its ability to perform any DNA repair functions. (frontiersin.org)
- Colocalisation of BARD1 with BRCA1 and RAD51 in response to DNA damage indicates a role in DNA repair, 19, 20 which is supported by the recent observation of BARD1 participation along with BRCA1 in homology directed repair of chromosome breaks. (bmj.com)
Germline2
- Real-world patient-reported outcomes and physician satisfaction with poly (ADP-ribose) polymerase inhibitors versus chemotherapy in patients with germline BRCA1/2-mutated human epidermal growth factor receptor 2-negative advanced breast cancer from the United States, Europe, and Israel. (jefferson.edu)
- Real-world study of patients with germline BRCA1/2-mutated human epidermal growth factor receptor 2?Negative advanced breast cancer: Patient demographics, treatment patterns, adverse events, and physician-reported satisfaction in the United States, Europe, and Israel. (jefferson.edu)
Human BRCA1 gene2
- The human BRCA1 gene is located on the long (q) arm of chromosome 17 at region 2 band 1, from base pair 41,196,312 to base pair 41,277,500 (Build GRCh37/hg19) (map). (wikipedia.org)
- A human BRCA1 gene knockout. (xenbase.org)
Interaction11
- The BARD1/BRCA1 interaction is disrupted by tumorigenic amino acid substitutions in BRCA1, implying that the formation of a stable complex between these proteins may be an essential aspect of BRCA1 tumor suppression. (wikipedia.org)
- In contrast to full-length BRCA1, Rdd-BRCA1 did not require BRCA1-associated RING domain 1 (BARD1) interaction for stability. (jci.org)
- These data strongly suggest that the ligase activity of BRCA1, through interaction with E2 and BARD1, is related to breast cancer predisposition. (biomedcentral.com)
- These data have been combined with Grantham variation and Grantham deviance scores (a measure of how conserved an amino acid is, together with how different the protein change is) to assess the relationship between protein:protein interaction and measures of disease risk. (biomedcentral.com)
- As evaluated by co-immunoprecipitation experiments, the dsDNA recombination function relates to the Redα-Redβ protein-protein interaction, which requires not only contacts in the C-terminal domain but also a region near the N-terminus. (nature.com)
- 1) How does the hereditary breast tumor suppressor BRCA1 interaction network suppress breast tumor development? (mdanderson.org)
- BARD1 was originally identified through its interaction with BRCA1, with which it has a closely related domain structure. (bmj.com)
- 21 Furthermore, interaction between the BARD1/BRCA1 heterodimer and cleavage stimulation factor subunit 1 (CSTF1, also called CstF-50) represses the polyadenylation machinery, presumably to prevent inappropriate mRNA processing at sites of DNA repair. (bmj.com)
- 26 The suggested role in TP53 dependent apoptotic signalling 27 and interaction with the ankyrin repeats of proto-oncoprotein BCL3, thereby possibly modulating the activity of transcription factor NFKB, 28 represent BRCA1 independent functions of BARD1. (bmj.com)
- Although BRCA1 interaction with key proteins involved in DNA repair is well known, its role as a co-regulator in the transcriptional response to DNA damage remains poorly understood. (conicet.gov.ar)
- Protein-protein interaction networks for FANCD2 were built using the STRING website. (bvsalud.org)
Genomic4
- 10 ng, 100 ng and 1 µg of purified genomic DNA was enriched using the NEBNext Direct BRCA1/BRCA2 Panel. (neb.com)
- Download DNA or protein sequence, view genomic context and coordinates. (yeastgenome.org)
- They also discuss how these proteins and pathways are strictly regulated to avoid genomic instability, which can lead to diseases such as cancer, and how they are coordinated with other nuclear processes (e.g., transcription and DNA replication). (cshlpress.com)
- Her laboratory worked to discover which proteins BRCA1 is targeting with ubiquitin and how that activity might help attenuate cell division in response to DNA damage - a function that is important for maintaining genomic integrity and suppressing tumor growth. (georgetown.edu)
Susceptibility3
- Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the BRCA1 (/ˌbrækəˈwʌn/) gene. (wikipedia.org)
- SUMO2 N-glycyl-lys BRCA1, Breast cancer type 1 susceptibility protein ecNumber6.3.2. (reactome.org)
- She called her discovery BRCA1 (breast cancer susceptibility gene 1) for its breast cancer connection. (yale.edu)
Molecular4
- Basic sequence-derived (length, molecular weight, isoelectric point) and experimentally-determined (median abundance, median absolute deviation) protein information. (yeastgenome.org)
- BRCA1 and BRCA2 are two proteins that play a critical role in this process, but scientists do not understand exactly how these proteins repair DNA at the molecular level. (againstbreastcancer.org.uk)
- Funciona como andamio molecular para localizar y estabilizar estas proteínas en los sitios de recombinación homóloga. (bvsalud.org)
- It functions as a molecular scaffold to localize and stabilize these proteins at homologous recombination sites. (bvsalud.org)
BARD17
- These four helices combine to form a heterodimerization interface and stabilize the BRCA1-BARD1 heterodimer complex. (wikipedia.org)
- BRCA1 polypeptides, in particular, Lys-48-linked polyubiquitin chains are dispersed throughout the resting cell nucleus, but at the start of DNA replication, they gather in restrained groups that also contain BRCA2 and BARD1. (wikipedia.org)
- 11 The functionally important BARD1/BRCA1 heterodimer formation is mediated by the RING finger motifs and has also been shown to markedly increase the stability of both proteins. (bmj.com)
- BARD1, unlike BRCA1, also contains a centrally located sequence of three ankyrin repeats 11 that are found in many proteins involved in transcriptional regulation. (bmj.com)
- 22, 23 The significance of BARD1/BRCA1 collaboration has also been emphasised by studies of its ubiquitin ligase activity that might contribute to tumour suppression and other biological functions of BRCA1. (bmj.com)
- 25 BARD1 also regulates the subcellular localisation of BRCA1, both by translocating BRCA1 into the nucleus and by inhibiting its nuclear export. (bmj.com)
- The phenotype of Bard1 null mice was found to be remarkably similar to that of Brca1 nulls, further emphasising the functional relationship between these two proteins. (bmj.com)
Tumor suppressor2
- BRCA1 is a human tumor suppressor gene (also known as a caretaker gene) and is responsible for repairing DNA. (wikipedia.org)
- There is a debate in the scientific community about whether BRCA1 enzymatic activity is important in tumor suppressor function," Yarden said. (georgetown.edu)
Peptides1
- BRCA1 peptides detected from MDA-MB-231 cells are highlighted in yellow and SUM1315MO2 RR1 cells in green, Met-297 is highlighted in red (below). (jci.org)
BRCT3
- The BRCA1 protein contains the following domains: Zinc finger, C3HC4 type (RING finger) BRCA1 C Terminus (BRCT) domain This protein also contains nuclear localization signals and nuclear export signal motifs. (wikipedia.org)
- the Znf C3HC4- RING domain, the BRCA1 serine domain and two BRCT domains. (wikipedia.org)
- 11 Both proteins possess an N-terminal RING finger motif and two BRCA1 C-terminal (BRCT) domains present in numerous proteins involved in DNA repair and cell cycle regulation. (bmj.com)
Response to DNA damage2
- The paper shows that in response to DNA damage, BRCA1 is responsible for tagging these two proteins to stop the cells from dividing so repair can occur," Yarden said. (georgetown.edu)
- Furthermore, we demonstrate that BRCA1 targets GADD153 promoter to increase its transcription in response to DNA damage. (conicet.gov.ar)
Ovarian3
- In addition, in some patients with a personal or family history of breast and ovarian cancer, the protective role of BRCA1 in DNA-copying is disabled - while its break repair function is still active. (birmingham.ac.uk)
- Individuals carrying a mutation in the breast cancer 1, early onset gene ( BRCA1 ) are at increased risk of breast or ovarian cancer and thus are candidates for risk reduction strategies such as oophorectomy and mastectomy. (jci.org)
- Plasma Protein Biomarkers Associated with Higher Ovarian Cancer Risk in BRCA1/2 Carriers. (cdc.gov)
Homology-direct1
- The BRCA2 R3052W mutated protein exacerbates genome instability, is unable to rescue homology-directed repair, and fails to complement cell survival following exposure to PARP inhibitors and crosslinking drugs. (frontiersin.org)
Functionally1
- Amino acid substitution during functionally constrained divergent evolution of protein sequences. (xenbase.org)
Sequence4
- Analysis of missense variation in human BRCA1 in the context of interspecific sequence variation. (xenbase.org)
- From a series of 20,000 full sequence tests of BRCA1 carried out at Myriad Genetic Laboratories, a total of 314 different missense changes and eight in-frame deletions were observed. (xenbase.org)
- Click "Protein Details" for further information about the protein such as half-life, abundance, domains, domains shared with other proteins, protein sequence retrieval for various strains, physico-chemical properties, protein modification sites, and external identifiers for the protein. (yeastgenome.org)
- These shared biochemical, protein sequence and functional similarities suggest the existence of an ancestral annealing mechanism involved in HR. (nature.com)
BRCA2 Protein1
- (A) BRCA2 protein schematic depicting domain organization: N-terminus, BRC repeats DNA binding domain (DBD), and C-terminal domain (CTD). (frontiersin.org)
Interactions3
- Currently, her projects mainly focus on studying BRCA2 and Tel1 related protein-protein interactions involved in DNA damage response pathway, using Cryo-EM and other biophysics methods. (imperial.ac.uk)
- Also, they share a similar protein architecture based on an N-terminal ssDNA binding domain of ~180 amino acids and a C-terminal extension that in the case of RAD52 is required for homologous recombination (HR) through specific protein-protein interactions 6 . (nature.com)
- The emerging picture of BRCA1 population genetics involves complex interactions of family history, age, and genetic ancestry, all of which should be taken into account when considering testing or interpreting results. (duke.edu)
Breast cancer11
- In normal cells the BRCA1 protein is localized in the nucleus, whereas in the majority of breast cancer cell lines and in malignant pleural effusions from breast cancer patients, it is localized mainly in the cytoplasm. (jefferson.edu)
- Kunwor R, Silver DP, Abu-Khalaf M. PARP Inhibitors for the Treatment of BRCA1/2-Mutated Metastatic Breast Cancer: A Systematic Review and Meta-analysis. (jefferson.edu)
- Real-World Study of Regional Differences in Patient Demographics, Clinical Characteristics, and BRCA1/2 Mutation Testing in Patients with Human Epidermal Growth Factor Receptor?2-Negative Advanced Breast Cancer in the United States, Europe, and Israel. (jefferson.edu)
- Clinicopathological features and BRCA1 and BRCA2 mutation status in a prospective cohort of young women with breast cancer. (jefferson.edu)
- These data extend our previous findings that breastfeeding protects against BRCA1-, but not BRCA2-associated breast cancer. (nih.gov)
- If BRCA1 or BRCA2 itself is damaged by a BRCA mutation, damaged DNA is not repaired properly, and this increases the risk for breast cancer. (wikipedia.org)
- In this study, we investigated the mechanisms that lead to PARPi and platinum resistance in the SUM1315MO2 breast cancer cell line, which harbors a hemizygous BRCA1 185delAG mutation. (jci.org)
- A BRCA1 mutation leads to breast cancer in 72 percent of women. (yale.edu)
- To date, inheritance of a mutant BRCA1 or BRCA2 gene is the best-established indicator of an increased risk of developing breast cancer. (jci.org)
- Scholars@Duke publication: Frequency of breast cancer attributable to BRCA1 in a population-based series of American women. (duke.edu)
- CONTEXT: Previous studies of BRCA1 mutation prevalence have been based on high-risk groups, yielding estimates that do not reflect the experience of the general population of US patients with breast cancer. (duke.edu)
Mass spectrometry1
- BRCA1 was immunoprecipitated from MDA-MB-231 and SUM1315MO2 RR1 cells and subjected to mass spectrometry. (jci.org)
Genetic2
- HRDetect was trained using machine learning methods to identify tumours that had BRCA1 or BRCA2 genetic defects. (thenakedscientists.com)
- So we can see the patterns, and the patterns look identical to BRCA1 or BRCA2 tumours, but we can't find the genetic defect. (thenakedscientists.com)
Homologous1
- Single strand annealing proteins (SSAPs) like Redβ initiate homologous recombination by annealing complementary DNA strands. (nature.com)
Targets1
- This histogram shows the percent of reads aligned to the human genome, and the percent of reads mapped to the targets included in the BRCA1/BRCA2 Panel across different input DNA amounts. (neb.com)
Involved in DNA repair1
- BRCA1 and BRCA2 are proteins that are involved in DNA repair. (thenakedscientists.com)
Genome integrity1
- BRCA1 plays numerous roles in the regulation of genome integrity and chemoresistance. (conicet.gov.ar)
Orthologs1
- BRCA1 orthologs have been identified in most vertebrates for which complete genome data are available. (wikipedia.org)
Cancer5
- We're examining BRCA1 and BRCA2 to understand the progression of cancer at the most fundamental level," said Dr. Ryan Jensen, Associate Professor of Therapeutic Radiology at Yale Medical School. (yale.edu)
- BRCA1 loss induces GADD153-mediated doxorubicin resistance in prostate cancer. (conicet.gov.ar)
- In this study we show that BRCA1 plays a central role in the transcriptional response to genotoxic stress in prostate cancer. (conicet.gov.ar)
- These findings define a novel transcriptional pathway through which BRCA1 orchestrates cell fate decisions in response to genotoxic insults, and suggest that BRCA1 status should be considered for new chemotherapeutic treatment strategies in prostate cancer. (conicet.gov.ar)
- E7 from human papil omavirus type 16 cooperate to cancer: the European prospective investigation into doi:10.1093/carcin/bgp321 PMID:20047954 target the PDZ protein Na/H exchange regulatory cancer and nutrition study. (who.int)
Motif1
- The BRCA1 RING motif is flanked by alpha helices formed by residues 8-22 and 81-96 of the BRCA1 protein. (wikipedia.org)
BAP13
- These samples were examined closely to find out if the BAP1 protein was missing and if the p16 gene had certain changes. (survivingmesothelioma.com)
- BAP1 Expression and Mesothelioma BAP1 stands for BRCA1 associated protein-1. (survivingmesothelioma.com)
- People who have an inherited mutation of this gene produce less of the BAP1 protein. (survivingmesothelioma.com)
Target proteins1
- Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant and ubiquitous nuclear protein that uses NAD + to synthesize a multibranched polyanion composed of ADP-ribose moieties, giving rise to poly(ADP-ribose) (PAR), onto itself or a variety of target proteins. (nature.com)
Subunit2
- It contains an N-terminal RING FINGER DOMAIN and is a PROTEIN PHOSPHATASE 1 regulatory subunit. (jefferson.edu)
- The nuclear localization sequences of the BRCA1 protein interact with the importin-alpha subunit of the nuclear transport signal receptor. (xenbase.org)
MeSH1
- BRCA1 Protein" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (jefferson.edu)
Clinical1
- Luke completed his D.Phil in Clinical Medicine at Oxford University (Merton College), but his research career has predominantly focused on investigating protein function using structural biology as a means to provide a mechanistic understanding in life and in disease. (imperial.ac.uk)
Allele1
- The BRCA1 185delAG allele is a common inherited mutation located close to the protein translation start site that is thought to produce a shortened, nonfunctional peptide. (jci.org)
Polymorphisms2
- BRCA1 polymorphisms. (xenbase.org)
- A recurring problem in the clinic is that many detectable changes within the BRCA1 gene produce subtle alterations to the protein that are not easily recognized as either harmful (loss-of-function) alleles or harmless and thus inconsequential polymorphisms. (jci.org)
Transcriptional1
- Thus, this protein plays a role in transcription, and DNA repair of double-strand DNA breaks ubiquitination, transcriptional regulation as well as other functions. (wikipedia.org)
Vectors1
- In this issue of the JCI , Chang, Sharan, and colleagues describe a novel system to evaluate human BRCA1 alleles for in vivo function using BACs containing human BRCA1 vectors in mouse cells and embryos (see the related article beginning on page 3160). (jci.org)
Tumour2
- HRDetect is trained to identify those patterns and tell you what the likelihood is of any tumour having a BRCA1 or BRCA2 type of defect. (thenakedscientists.com)
- He aims to further understand which regions of the BRCA1 and BRCA2 proteins are essential for repairing DNA damage and preventing tumour formation. (againstbreastcancer.org.uk)
Overexpression1
- Ectopic overexpression of Rdd-BRCA1 promoted partial PARPi and cisplatin resistance. (jci.org)
Contains an N-terminal1
- A Fanconi anemia complementation group protein that contains an N-terminal DNA-binding region and seven, C-terminal, WD REPEATS. (bvsalud.org)
Nuclear3
- May also act as a cytoplasmic retention protein with a role in regulating nuclear transport. (nih.gov)
- The protein encoded by this gene was identified by its ability to bind to the nuclear localization signal of BRCA1 and other proteins. (nih.gov)
- It is a cytoplasmic protein which may regulate nuclear targeting by retaining proteins with a nuclear localization signal in the cytoplasm. (nih.gov)
Expression4
- rather, PARPi and platinum resistance required increased expression of a really interesting gene (RING) domain-deficient BRCA1 protein (Rdd-BRCA1). (jci.org)
- Brca1 expression is regulated by a bidirectional promoter that is shared by the Nbr1 gene in mouse. (nih.gov)
- Binding of this protein to CXCR3 results in pleiotropic effects, including stimulation of monocytes, natural killer and T-cell migration, and modulation of adhesion molecule expression. (cancerindex.org)
- BRCA1 expression mediates apoptosis, cell cycle arrest and decreased viability in response to doxorubicin treatment. (conicet.gov.ar)
Workflow1
- He is working on developing a workflow for prototyping proteins using cell-free systems and machine learning. (imperial.ac.uk)