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BRCA1 And BRCA2 Mutations And Absolute Cancer Risk
Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the ''BRCA1'' () gene. Orthologs are common in other vertebrate species, whereas invertebrate genomes may encode a more distantly related gene. ''BRCA1'' is a human tumor suppressor gene (also known as a caretaker gene) and is responsible for repairing DNA. ''BRCA1'' and ''BRCA2'' are unrelated proteins, but both are normally expressed in the cells of breast and other tissues, where they help repair damaged DNA, or destroy cells if DNA cannot be repaired. They are involved in the repair of chromosomal damage with an important role in the error-free repair of DNA double-strand breaks. 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. ''BRCA1'' and ''BRCA2'' have been described as "breast cancer susceptibility genes" and "breast cancer susceptibility proteins". The predominant allele has a normal, ...
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Protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metabolic reactions, DNA replication, Cell signaling, responding to stimuli, providing Cytoskeleton, structure to cells and Fibrous protein, organisms, and Intracellular transport, transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the Nucleic acid sequence, nucleotide sequence of their genes, and which usually results in protein folding into a specific Protein structure, 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called pep ...
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RNA Polymerase II
RNA polymerase II (RNAP II and Pol II) is a Protein complex, multiprotein complex that Transcription (biology), transcribes DNA into precursors of messenger RNA (mRNA) and most small nuclear RNA (snRNA) and microRNA. It is one of the three RNA polymerase, RNAP enzymes found in the nucleus of eukaryote, eukaryotic cells. A 550 kDa complex of 12 subunits, RNAP II is the most studied type of RNA polymerase. A wide range of transcription factors are required for it to bind to upstream gene promoter (biology), promoters and begin transcription. Discovery Early studies suggested a minimum of two RNAPs: one which synthesized rRNA in the nucleolus, and one which synthesized other RNA in the nucleoplasm, part of the nucleus but outside the nucleolus. In 1969, biochemists Robert G. Roeder and William J. Rutter, William Rutter discovered there are total three distinct nuclear RNA polymerases, an additional RNAP that was responsible for transcription of some kind of RNA in the nucleoplasm. ...
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Nuclear Localization Signal
A nuclear localization signal ''or'' sequence (NLS) is an amino acid sequence that 'tags' a protein for import into the cell nucleus by nuclear transport. Typically, this signal consists of one or more short sequences of positively charged lysines or arginines exposed on the protein surface. Different nuclear localized proteins may share the same NLS. An NLS has the opposite function of a nuclear export signal (NES), which targets proteins out of the nucleus. Types Classical These types of NLSs can be further classified as either monopartite or bipartite. The major structural differences between the two are that the two basic amino acid clusters in bipartite NLSs are separated by a relatively short spacer sequence (hence bipartite - 2 parts), while monopartite NLSs are not. The first NLS to be discovered was the sequence PKKKRKV in the SV40 Large T-antigen (a monopartite NLS). The NLS of nucleoplasmin, KR AATKKAGQAKKK, is the prototype of the ubiquitous bipartite signal: two ...
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BRCT Domain
BRCA1 C Terminus (BRCT) domain is a family of evolutionarily related proteins. It is named after the C-terminal domain of BRCA1, a DNA-repair protein that serves as a marker of breast cancer susceptibility. The BRCT domain is found predominantly in proteins involved in cell cycle checkpoint functions responsive to DNA damage, for example as found in the breast cancer DNA-repair protein BRCA1. The domain is an approximately 100 amino acid tandem repeat, which appears to act as a phospho-protein binding domain. Examples Human proteins containing this domain include: * BARD1; BRCA1 * CTDP1; TDT or DNTT * ECT2 * LIG4 * MCPH1; MDC1 * NBN * PARP1; PARP4; PAXIP1; PES1 * REV1; RFC1; TOPBP1 DNA topoisomerase 2-binding protein 1 (TOPBP1) is a scaffold protein that in humans is encoded by the ''TOPBP1'' gene. TOPBP1 was first identified as a protein binding partner of DNA TOP2B, topoisomerase-IIβ by a Two-hybrid screening, yeast 2- ...; TP53BP1; XRCC1 References ...
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RING Finger Domain
In molecular biology, a RING (short for Really Interesting New Gene) finger domain is a protein structural domain of zinc finger type which contains a C3HC4 amino acid motif which binds two zinc cations (seven cysteines and one histidine arranged non-consecutively). This protein domain contains 40 to 60 amino acids. Many proteins containing a RING finger play a key role in the ubiquitination pathway. Conversely, proteins with RING finger domains are the largest type of ubiquitin ligases in the human genome. Zinc fingers Zinc finger (Znf) domains are relatively small protein motifs that bind one or more zinc atoms, and which usually contain multiple finger-like protrusions that make tandem contacts with their target molecule. They bind DNA, RNA, protein and/or lipid substrates. Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains a ...
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Orthologs
Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a speciation event (orthologs), or a duplication event (paralogs), or else a horizontal (or lateral) gene transfer event (xenologs). Homology among DNA, RNA, or proteins is typically inferred from their nucleotide or amino acid sequence similarity. Significant similarity is strong evidence that two sequences are related by evolutionary changes from a common ancestral sequence. Alignments of multiple sequences are used to indicate which regions of each sequence are homologous. Identity, similarity, and conservation The term "percent homology" is often used to mean "sequence similarity”, that is the percentage of identical residues (''percent identity''), or the percentage of residues conserved with similar physicochemical properties ('' ...
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University Of California, Berkeley
The University of California, Berkeley (UC Berkeley, Berkeley, Cal, or California), is a Public university, public Land-grant university, land-grant research university in Berkeley, California, United States. Founded in 1868 and named after the Anglo-Irish philosopher George Berkeley, it is the state's first land-grant university and is the founding campus of the University of California system. Berkeley has an enrollment of more than 45,000 students. The university is organized around fifteen schools of study on the same campus, including the UC Berkeley College of Chemistry, College of Chemistry, the UC Berkeley College of Engineering, College of Engineering, UC Berkeley College of Letters and Science, College of Letters and Science, and the Haas School of Business. It is Carnegie Classification of Institutions of Higher Education, classified among "R1: Doctoral Universities – Very high research activity". Lawrence Berkeley National Laboratory was originally founded as par ...
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Mary-Claire King
Mary-Claire King (born February 27, 1946) is an American geneticist. She was the first to show that breast cancer can be inherited due to mutations in the gene she called ''BRCA1''. She studies human genetics and is particularly interested in genetic heterogeneity and complex traits. She studies the interaction of genetics and environmental influences and their effects on human conditions such as breast and ovarian cancer, inherited deafness, schizophrenia, HIV, systemic lupus erythematosus and rheumatoid arthritis. She has been the American Cancer Society Professor of the Department of Genome Sciences and of Medical Genetics at the University of Washington School of Medicine since 1995. Besides known for her accomplishment in identifying breast cancer genes, King is also known for demonstrating that humans and chimpanzees are 99% genetically identical and for applying genomic sequencing to identify victims of human rights abuses. In 1984, in Argentina, she began working in ide ...
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Association For Molecular Pathology V
Association may refer to: *Club (organization), an association of two or more people united by a common interest or goal *Trade association, an organization founded and funded by businesses that operate in a specific industry *Voluntary association, a body formed by individuals to accomplish a purpose, usually as volunteers * Non profit association, a body formed by individuals to accomplish a purpose without any profit interest *Collaboration, the act of working together Association in various fields of study *Association (archaeology), the close relationship between objects or contexts. * Association (astronomy), combined or co-added group of astronomical exposures * Association (chemistry) *Association (ecology), a type of ecological community *Genetic association, when one or more genotypes within a population co-occur *Association (object-oriented programming), defines a relationship between classes of objects *Association (psychology), a connection between two or more conce ...
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Myriad Genetics
Myriad Genetics, Inc. is an American genetic testing and precision medicine company based in Salt Lake City, Utah, United States. Myriad employs a number of proprietary technologies that permit doctors and patients to understand the genetic basis of human disease and the role that genes play in the onset, progression and treatment of disease. This information is used to guide the development of new products that assess an individual's risk for developing disease later in life (predictive medicine), identify a patient's likelihood of responding to a particular drug therapy (precision medicine), assess a patient's risk of disease progression and disease recurrence (precision medicine), and measure disease activity. History The global search for the genetic basis of breast cancer began when Mary-Claire King, Ph.D., from the University of California, Berkeley announced the localization through linkage analysis of a gene associated with increased risk for breast cancer (BRCA1) to t ...
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Biological Patent
Biology is the scientific study of life and living organisms. It is a broad natural science that encompasses a wide range of fields and unifying principles that explain the structure, function, growth, origin, evolution, and distribution of life. Central to biology are five fundamental themes: the cell as the basic unit of life, genes and heredity as the basis of inheritance, evolution as the driver of biological diversity, energy transformation for sustaining life processes, and the maintenance of internal stability ( homeostasis). Biology examines life across multiple levels of organization, from molecules and cells to organisms, populations, and ecosystems. Subdisciplines include molecular biology, physiology, ecology, evolutionary biology, developmental biology, and systematics, among others. Each of these fields applies a range of methods to investigate biological phenomena, including observation, experimentation, and mathematical modeling. Modern biology is gr ...
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Transcriptional Regulation
In molecular biology and genetics, transcriptional regulation is the means by which a cell regulates the conversion of DNA to RNA ( transcription), thereby orchestrating gene activity. A single gene can be regulated in a range of ways, from altering the number of copies of RNA that are transcribed, to the temporal control of when the gene is transcribed. This control allows the cell or organism to respond to a variety of intra- and extracellular signals and thus mount a response. Some examples of this include producing the mRNA that encode enzymes to adapt to a change in a food source, producing the gene products involved in cell cycle specific activities, and producing the gene products responsible for cellular differentiation in multicellular eukaryotes, as studied in evolutionary developmental biology. The regulation of transcription is a vital process in all living organisms. It is orchestrated by transcription factors and other proteins working in concert to finely tune t ...
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