Assessment of human Nter and Cter BRCA1 mutations using growth and localization assays in yeast.

Details

Serval ID
serval:BIB_35AD1B0D1EE4
Type
Article: article from journal or magazin.
Collection
Publications
Title
Assessment of human Nter and Cter BRCA1 mutations using growth and localization assays in yeast.
Journal
Human mutation
Author(s)
Millot G.A., Berger A., Lejour V., Boulé J.B., Bobo C., Cullin C., Lopes J., Stoppa-Lyonnet D., Nicolas A.
ISSN
1098-1004 (Electronic)
ISSN-L
1059-7794
Publication state
Published
Issued date
12/2011
Peer-reviewed
Oui
Volume
32
Number
12
Pages
1470-1480
Language
english
Notes
Publication types: Evaluation Study ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
A large number of missense mutations have been identified within the tumor suppressor gene BRCA1. Most of them, called "variants of unknown significance" (VUS), cannot be classified as pathogenic or neutral by genetic methods, which complicates their cancer risk assessment. Functional assays have been developed to circumvent this uncertainty. They aim to determine how VUS impact the BRCA1 protein structure or function, thereby giving an indication of their potential to cause cancer. So far, three relevant assays have been designed in yeast and used on large sets of variants. However, they are limited to variants mapped in restricted domains of BRCA1. One of them, the small colony phenotype (SCP) assay, monitors the BRCA1-dependent growth of yeast colonies that increases with pathogenic but not neutral mutations positioned in the Cter region. Here, we extend this assay to the Nter part of BRCA1. We also designed a new assay, called the "yeast localization phenotype (YLP) assay," based on the accumulation of BRCA1 in a single inclusion body in the yeast nucleus. This phenotype is altered by variants positioned both in the Nter and Cter regions. Together, these assays provide new perspectives for the functional assessment of BRCA1 mutations in yeast.
Keywords
BRCA1 Protein/chemistry, BRCA1 Protein/genetics, BRCA1 Protein/metabolism, Biological Assay/methods, Breast Neoplasms/genetics, Breast Neoplasms/physiopathology, Cell Nucleus/metabolism, Cell Nucleus/ultrastructure, Female, Genes, BRCA1, Genetic Predisposition to Disease, Genetic Variation, Humans, Inclusion Bodies/metabolism, Mutation, Phenotype, Saccharomyces cerevisiae/genetics, Saccharomyces cerevisiae/growth & development, Saccharomyces cerevisiae/metabolism
Pubmed
Web of science
Create date
15/07/2020 10:12
Last modification date
16/07/2020 8:43
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