Toward classification of BRCA1 missense variants using a biophysical approach.

ABSTRACT: Carriers of germ line mutations in breast cancer susceptibility gene BRCA1 have an increased risk of developing breast and ovarian cancers; missense mutations have, however, been difficult to assess for disease association. Here we have used a biophysical approach to classify these variants. We established an assay for measuring the thermodynamic stability of the BRCA1 BRCT domains and investigated the effects of 36 missense mutations. The mutations show a range of effects. Some do not change the stability, whereas others destabilize the protein by as much as 6 kcal mol(-1); one-third of the mutants could not be expressed in soluble form in Escherichia coli, and we conclude that these destabilize the protein by an even greater amount. We tested several computer algorithms for their ability

SUBMITTER: Rowling PJ 

PROVIDER: S-EPMC2888420 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature