NDLI: Human BRCA1 inhibits growth in yeast: potential use in diagnostic testing.

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Human BRCA1 inhibits growth in yeast: potential use in diagnostic testing.

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Human BRCA1 inhibits growth in yeast: potential use in diagnostic testing.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Humphrey, J. S. Erdos, M. R. Collins, F. S. Klausner, R. D. Brody, L. C. Salim, A.
Description	Author Affiliation: Humphrey JS ( Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. jshumphr@helix.nih.gov);
Abstract	Germline-inactivating mutations of BRCA1 result in a hereditary predisposition to breast and ovarian cancer. Truncating mutations of BRCA1 predispose to cancer and can be ascertained by protein truncation testing or sequencing. However, cancer-predisposing missense mutations of BRCA1 are difficult to distinguish from polymorphisms by genetic testing methods currently used. Here we show that expression of BRCA1 or BRCA1 fused to a GAL4 activation domain in Saccharomyces cerevesiae inhibits growth, resulting in small colonies easily distinguishable from vector-transformed controls. The growth inhibitory effect can be localized to sequences encoding the recently described BRCA1 C-terminal domains. Growth suppression by a BRCA1 fusion protein is not influenced by introduction of neutral polymorphisms but is diminished or abolished by frameshift, nonsense, or disease-associated missense mutations located in the C-terminal 305 amino acids of BRCA1. These observations may permit the functional significance of many BRCA1 sequence changes to be assessed in yeast. Additionally, the correlation of growth suppression with wild-type forms of BRCA1 suggests that the assay may be capable of detecting functionally conserved interactions between the evolutionarily conserved BRCA1 C-terminal domains and cellular elements found in both human and yeast cells.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	11
Volume Number	94
Language	English
Publisher	National Academy of Sciences
Publisher Date	1997-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	BRCA1 Protein Pharmacology Tumor Markers, Biological Saccharomyces Cerevisiae Proteins Saccharomyces Cerevisiae Growth & Development Transcription Factors Biosynthesis Blotting, Western Breast Neoplasms Diagnosis Genetics DNA-Binding Proteins Fungal Proteins Galactose Gene Expression Drug Effects Ovarian Neoplasms Polymorphism, Genetic Recombinant Fusion Proteins Sequence Deletion Time Factors Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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