Functional differences among BRCA1 missense mutations in the control of centrosome duplication.

ABSTRACT: We analyzed the effects of 14 different missense mutations in the RING domain of BRCA1 on the function of the protein in the control of centrosome number in tissue culture cells. Whereas 2 of the 14 BRCA1 variant proteins were neutral in the centrosome duplication assay, missense mutations of zinc-coordinating residues (C24R, C27A, C39Y, H41F, C44F and C47G) and mutations encoding BRCA1 variants M18T and I42V resulted in BRCA1 proteins that caused centrosome amplification. BRCA1 variant proteins I21V, I31M, L52F and D67Y had an intermediate effect on centrosome duplication. In addition, one of the variants, L52F, caused a peculiar phenotype with amplified centrosomes but the centrioles remained paired. By comparison, other BRCA1 variants that caused centrosome amplification had clustering

SUBMITTER: Kais Z 

PROVIDER: S-EPMC4222025 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature