BRCA1 and BRCA2: breast/ovarian cancer susceptibility gene products and participants in DNA double-strand break repair.
ABSTRACT BRCA1 and BRCA2 are tumor suppressor genes, familial mutations in which account for approximately 5% of breast cancer cases in the USA annually. Germ line mutations in BRCA1 that truncate or inactivate the protein lead to a cumulative risk of breast cancer, by age 70, of up to 80%, whereas the risk of ovarian cancer is 30-40%. For germ line BRCA2 mutations, the breast cancer cumulative risk approaches 50%, whereas for ovarian cancers, it is between 10 and 15%. Both BRCA1 and BRCA2 are involved in maintaining genome integrity at least in part by engaging in DNA repair, cell cycle checkpoint control and even the regulation of key mitotic or cell division steps. Unsurprisingly, the complete loss of function of either protein leads to a dramatic increase in genomic instability. How they function in maintaining genome integrity after the onset of DNA damage will be the focus of this review.
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ABSTRACT: The maintenance of chromosomal integrity is an essential task of every living organism and cellular repair mechanisms exist to guard against insults to DNA. Given the importance of this process, it is expected that DNA repair proteins would be evolutionarily conserved, exhibiting very minimal sequence change over time. However, BRCA1, an essential gene involved in DNA repair, has been reported to be evolving rapidly despite the fact that many protein-altering mutations within this gene convey a significantly elevated risk for breast and ovarian cancers.BMC Evolutionary Biology 07/2014; 14(1):155. · 3.41 Impact Factor
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ABSTRACT: Genomic instability finally induces cell death or apoptosis. The tumor suppressor, phosphatase and tensin homolog on chromosome 10 (PTEN), is a dual-specificity phosphatase, which has protein phosphatase activity and lipid phosphatase activity that antagonizes PI3K activity. Cells that lack PTEN have constitutively higher levels of PIP3 and activated downstream PI3K/AKT targets. BRCA1, a well-known breast cancer tumor suppressor, is to associate with breast cancer risk and genetic susceptibility. Many studies have demonstrated that PTEN, as well as BRCA1, plays a critical role in DNA damage responses. The BRCA1 functionally cooperates with PTEN and might be an essential blockage in the development of several tumors. Actually, the PTEN and BRCA1 genes are recognized as one of the most frequently deleted and/or mutated in many human cancers. The PI3K/AKT pathway is constitutively active in BRCA1-defective human cancer cells. Loss or decrease of these PTEN or BRCA1 function, by either mutation or reduced expression, has a role in various tumor developments. This review summarizes recent findings of the function of BRCA1 and PTEN involved in genomic stability and cancer cell signaling.Frontiers in Oncology 11/2014; 4:318.
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ABSTRACT: The recent US Supreme Court decision in Association for Molecular Pathology v. Myriad Genetics, Inc. clarified what is considered patentable subject matter. Patent claims limited to the composition of isolated nucleic acid sequences are now considered a product of nature and not patent eligible, while man-made variants of nucleic acid sequences may still be patentable. The decision is consistent with an earlier ruling in Mayo Collaborative Services v. Prometheus Laboratories., Inc. related to diagnostic methods. In Prometheus, the Court held that a method simply reciting known steps used to observe a natural event is not patentable subject matter. Taken together, the Court's decisions provide guidance as to what constitutes a natural phenomenon outside patent protection and what is considered a man-made creation worthy of protection. Despite misgivings, both decisions will provide impetus for increased genetic research and development of new therapeutics and diagnostics, especially in genomic and personalized medicine.ACS Medicinal Chemistry Letters 08/2013; 4(8):681-3. · 3.07 Impact Factor