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Fam Cancer. 2006;5(1):89-93.

Insights into the molecular basis of human hereditary breast cancer from studies of the BRCA1 BRCT domain.

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1
Department of Biochemistry, University of Alberta, T6G 2H7, Edmonton, AB, Canada. mark.glover@ualberta.ca

Abstract

The C-terminal, BRCT repeats of BRCA1 are essential for the tumor suppressor function of this protein. Here we review structural and functional studies of this domain. Both repeats adopt similar folds and pack in an intimate, head-to-tail manner. The domain binds phosphorylated targets such as the DNA damage-associated kinase BACH1, with a specificity for pSer-X-X-Phe motifs. Structural studies reveal that the N-terminal repeat is responsible for pSer binding while a groove at the interface of the two repeats recognizes the Phe. Missense variants identified in breast cancer screening programs often disrupt these interactions and these molecular defects may lead to an increased cancer risk.

PMID:
16528612
DOI:
10.1007/s10689-005-2579-z
[Indexed for MEDLINE]
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