The BRCA1-associated protein BACH1 is a DNA helicase targeted by clinically relevant inactivating mutations
Authors
Cantor, Sharon B.Drapkin, Ronny
Zhang, Fan
Lin, Yafang
Han, Juliana
Pamidi, Sushmita
Livingston, David M.
Document Type
Journal ArticlePublication Date
2004-02-26Keywords
Adenosine TriphosphatasesAmino Acid Substitution
BRCA1 Protein
Basic-Leucine Zipper Transcription Factors
DNA Helicases
Fanconi Anemia Complementation Group Proteins
Germ-Line Mutation
Humans
Leucine Zippers
Mutagenesis, Site-Directed
Nuclear Proteins
Transcription Factors
Amino Acids, Peptides, and Proteins
Cancer Biology
Genetic Phenomena
Neoplasms
Metadata
Show full item recordAbstract
BACH1 is a nuclear protein that directly interacts with the highly conserved, C-terminal BRCT repeats of the tumor suppressor, BRCA1. Mutations within the BRCT repeats disrupt the interaction between BRCA1 and BACH1, lead to defects in DNA repair, and result in breast and ovarian cancer. BACH1 is necessary for efficient double-strand break repair in a manner that depends on its association with BRCA1. Moreover, some women with early-onset breast cancer and no abnormalities in either BRCA1 or BRCA2 carry germline BACH1 coding sequence changes, suggesting that abnormal BACH1 function contributes to tumor induction. Here, we show that BACH1 is both a DNA-dependent ATPase and a 5'-to-3' DNA helicase. In two patients with early-onset breast cancer who carry distinct germline BACH1 coding sequence changes, the resulting proteins are defective in helicase activity, indicating that these sequence changes disrupt protein function. These results reinforce the notion that mutant BACH1 participates in breast cancer development.Source
Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2357-62.
DOI
10.1073/pnas.0308717101Permanent Link to this Item
http://hdl.handle.net/20.500.14038/26306PubMed ID
14983014Related Resources
ae974a485f413a2113503eed53cd6c53
10.1073/pnas.0308717101
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