BRCA1 exon 11 alternative splicing, multiple functions and the association with cancer.
نویسندگان
چکیده
BRCA1 (breast cancer early-onset 1) alternative splicing levels are regulated in a cell-cycle- and cell-type-specific manner, with splice variants being present in different proportions in tumour cell lines as well as in normal mammary epithelial cells. The importance of this difference in the pathogenesis of breast cancer has yet to be determined. Developing an understanding of the impact of BRCA1 isoform ratio changes on cell phenotype will be of value in breast cancer and may offer therapeutic options. In the present paper, we describe the splicing isoforms of BRCA1 exon 11, their possible role in cancer biology and the importance of maintaining a balanced ratio.
منابع مشابه
Evolutionary Constraint Helps Unmask a Splicing Regulatory Region in BRCA1 Exon 11
BACKGROUND Alternative splicing across exon 11 produces several BRCA1 isoforms. Their proportion varies during the cell cycle, between tissues and in cancer suggesting functional importance of BRCA1 splicing regulation around this exon. Although the regulatory elements driving exon 11 splicing have never been identified, a selective constraint against synonymous substitutions (silent nucleotide...
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Nonfluorescent labels were used for an array-format multiplex detection of alternative splice junctions of breast cancer susceptibility gene 1 (BRCA1) by surface-enhanced Raman scattering (SERS). A four-plex detection scheme using nonfluorescent labels was demonstrated for DNA sequences specific to four BRCA1 alternative splice variants: Delta(11q) (the last 3309 nt deleted from exon 11), Delta...
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متن کاملBRCA1 Exon 11, a CERES (Composite Regulatory Element of Splicing) Element Involved in Splice Regulation
Unclassified variants (UV) of BRCA1 can affect normal pre-mRNA splicing. Here, we investigate the UV c.693G>A, a "silent" change in BRCA1 exon 11, which we have found induces aberrant splicing in patient carriers and in vitro. Using a minigene assay, we show that the UV c.693G>A has a strong effect on the splicing isoform ratio of BRCA1. Systematic site-directed mutagenesis of the area surround...
متن کاملشناسایی جهش های جدید در اگزون 11 ژنBRCA1 در بیماران مبتلا به سرطان پستان ارثی
Introduction: Breast cancer is the most common malignancy in women worldwide. BRCA1 is a tumor suppressor gene that is involved in DNA-damage repair. One of the significant risk factors of breast cancer is the family history. BRCA1 gene consists of 24 exons that encode a protein with 1863 amino acids. Exon 11 is the largest exons and most of the disease-linked mutations have been found in it. I...
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عنوان ژورنال:
- Biochemical Society transactions
دوره 40 4 شماره
صفحات -
تاریخ انتشار 2012