Title
The BRCA1-associated protein BACH1 is a DNA helicase targeted by clinically relevant inactivating mutations
UMMS Affiliation
Department of Cancer Biology; Program in Molecular Medicine
Publication Date
2004-02-26
Document Type
Article
Subjects
Adenosine Triphosphatases; Amino 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
Disciplines
Amino Acids, Peptides, and Proteins | Cancer Biology | Genetic Phenomena | Neoplasms
Abstract
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.
DOI of Published Version
10.1073/pnas.0308717101
Source
Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2357-62.
Journal/Book/Conference Title
Proceedings of the National Academy of Sciences of the United States of America
Related Resources
PubMed ID
14983014
Repository Citation
Cantor SB, Drapkin R, Zhang F, Lin Y, Han J, Pamidi S, Livingston DM. (2004). The BRCA1-associated protein BACH1 is a DNA helicase targeted by clinically relevant inactivating mutations. Cancer Biology Publications. https://doi.org/10.1073/pnas.0308717101. Retrieved from https://escholarship.umassmed.edu/cancerbiology_pp/5